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Valentina Celoria,* Francois Rosset,* Valentina Pala, Paolo Dapavo, Simone Ribero, Pietro Quaglino, Luca Mastorino Dermatologic Clinic, Department of Medical Sciences, University of Turin, Turin, Italy*These authors contributed equally to this workCorrespondence: Valentina Celoria, Dermatologic Clinic, Department of Medical Sciences, University of Turin, Turin, Italy, Email valentina.celoria@edu.unito.itAbstract: 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.Keywords: psoriasis, skin microbiome, new therapies, gut microbiome, molecular precision medicines, next generation treatments

Gabriele Roccuzzo,* Luca Mastorino,* Giuseppe Gallo, Paolo Fava, Simone Ribero, Pietro Quaglino Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy*These authors contributed equally to this workCorrespondence: Giuseppe Gallo, Department of Medical Sciences, Section of Dermatology, University of Turin, Via Cherasco 23, Torino, Turin, 10126, Italy, Tel +39 0116335843 ; +39 0116335034, Email giuseppegallomd@gmail.comIntroduction: Folliculotropic mycosis fungoides (FMF) is the most frequent variant of mycosis fungoides (MF), with clinical features which differ from the classic form. As for therapeutic options, the latest guidelines on MF agree on a stage-driven strategy, in consideration of clinical presentation, symptom burden and patient’s comorbidities.Materials and Methods: A search on MEDLINE, PubMed, Scopus and Cochrane Library was conducted to gather the latest evidence on FMF clinical management. Manuscripts published in the last five years (January 2017–April 2022) were included. Our single-center experience was also described.Results: A total of 15 articles were analyzed, with a total of 432 patients (disease stage from IA to IVA2). The most widely-used treatment was psoralen ultra-violet A (PUVA) in monotherapy or in association with other drugs. Oral retinoid-based therapy was also described as a therapeutic option alone or in combination. Other therapy reported were based on Brentuximab Vedotin, Mogamulizumab, Carmustine, topical steroids, tazarotene and excimer laser, interferon, nitrogen mustard, imiquimod, systemic chemotherapy, extracorporeal photopheresis and stem cell transplantation.Discussion: FMF is characterized by specific clinical-pathologic features. Advanced forms assume characteristics more similar to classic MF (infiltrated plaques and nodules), whilst early stages can present in a wide range of clinical forms (acneiform lesions, follicular-like keratoses, erythematous patches). As for therapeutic options, in absence of specific guidelines, a high number of treatments are described in clinical practice, with variable results. Phototherapy in all its forms, especially as PUVA, appears to have the greatest initial therapeutic success. Retinoids, although widely used, appear to be poorly effective in monotherapy, particularly acitretin. Combination treatment with phototherapy seems to be advisable. Ionizing treatments, such as radiotherapy and TSEBT, appear effective, at least in the short term. Overall, an integrated approach is mandatory for the inconstant course of the disease and its multidisciplinary nature.Keywords: mycosis fungoides, folliculotropic mycosis fungoides, cutaneous lymphoma, primary cutaneous T-cell lymphoma, therapy

Introduction: Ixekizumab proved to be effective and safe for psoriasis treatment in several randomized clinical trials and real‐life studies. Nevertheless, long‐term real‐world experiences are still lacking, with little data up to 4 years of treatment. Objectives: To analyse survival, effectiveness and safety of ixekizumab in a real‐life cohort of patients affected by moderate‐to‐severe psoriasis or psoriatic arthritis up to 260 weeks (5 years). Methods: We included all patients treated with ixekizumab from December 2017 to March 2021. Drug survival (DS) was analysed in patients at risk for up to 5 years. Cox analysis was adopted to evaluate possible predictive factors of discontinuation. Psoriasis Area Severity Index (meanPASI and PASI100, 90, and ≤3) was used as outcomes of effectiveness on observed patients at 16, 52, 104, 156, 208 and 260 weeks. Logistic regression was performed to identify possible predictive factors of response. Results: DS was 65.5% at 260 weeks, with being a super‐responder patient (achievement of PASI100 at 16 weeks and maintained at 28 weeks) correlated with less risk of discontinuation. PASI100, 90 and ≤3 was achieved by 54.1%, 60.5% and 73% of observed patients, respectively, at 16 weeks, and by 59.1%, 81.8% and 95.5%, respectively, at 260 weeks. High mean BMI was the only factor strongly associated with less achievement of the outcomes at the earlier time points: PASI100 at 16 weeks (OR 0.93, CI 0.87–0.98, p = 0.014) and at 104 weeks (OR 0.91, CI 0.84–0.98, p = 0.019), PASI90 achievement at 16 weeks (OR 0.94, CI 0.88–0.99, p = 0.028) and 104 weeks (OR 0.91, CI 0.83–0.99, p = 0.027), and PASI ≤3 (OR 0.86, CI 0.76–0.97, p = 0.018) at 104 weeks. No severe adverse events were observed. Conclusions: Ixekizumab showed high effectiveness and safety for up to 5 years, with survival of 2/3 of treated patients. Rapid response to treatment is predictive of long‐term response. [ABSTRACT FROM AUTHOR]

This article is a response to a letter by Dr. Yu and Cheng-Chun Wei regarding the efficacy of anti-IL-23 and anti-IL-17 treatments after adalimumab failure in psoriatic patients. The authors agree with the lack of real-life studies comparing the rapidity of action and drug survival between IL-17 and IL-23 inhibitors. They provide data suggesting a higher survival rate for IL-23 inhibitors compared to TNF alpha inhibitors and IL-17 inhibitors. The authors also acknowledge the need for studies on the prevention of psoriasis-associated comorbidities and the inclusion of diverse ethnic groups in research. However, they note that their study was conducted in a university hospital in Northern Italy and had limited representation of non-Caucasian populations. They encourage researchers in other countries to share their experiences to better understand the response to biological treatments in different ethnic groups. [Extracted from the article]

Ixekizumab showed significantly higher efficacy in terms of PASI 90 at week 24, and a higher superiority of PASI 90 and PASI 100 also at week 48. In bio-naive patients, we found a significantly higher rate of PASI-90, PASI < 3 and PASI-100 with ixekizumab compared to the secukinumab ( I P i < 0.05), while in bio-experienced patients no significant difference was observed. There was no difference between the two drug survival curves among the two treatment arms. gl PASI-90 and PASI-100 response rates were achieved at week 12 by 124 (48%) and 108 (42%) in the secukinumab group ( I P i = 0.001), while 118 (64%) and 100 (54%) in the ixekizumab group ( I P i = 0.014) respectively (Figure 1b). [Extracted from the article]

Introduction: Palmoplantar psoriasis (PPp) has a profound negative impact on patients' quality of life, and it represents a therapeutic challenge, as palms and soles are difficult to treat area. Although the efficacy profile of tildrakizumab has been well evaluated in the literature, data on its use for PPp are still limited. The objective of the study was to evaluate the efficacy and safety of tildrakizumab on moderate-to-severe plaque psoriasis with involvement of the palmoplantar area., Methods: A multicenter, retrospective, real-life study was performed enrolling patients with moderate-to-severe plaque psoriasis involving the palmoplantar area undergoing treatment with tildrakizumab with a follow-up of at least 52 weeks. At baseline, demographic and clinical data were assessed. Psoriasis severity was evaluated by using Psoriasis Activity Severity Index (PASI), body surface area (BSA), Psoriasis Global Assessment (PGA), Pruritus-Numerical Rating Scale (P-NRS) and Dermatology Life Quality Index (DLQI). Palmoplantar PASI (ppPASI) was used to evaluate psoriasis severity in the palmoplantar region. Clinical improvement was evaluated at each follow-up visit [week (W) 4, 16, 52]., Results: A total of 99 patients were enrolled. A reduction in PASI, BSA, PGA, P-NRS and DLQI was observed at each time point. Mean ppPASI at baseline was 16.9 ± 13.2, which started to improve at W4 (8.9 ± 9.1) and continued to decrease at W16 (2.1 ± 3.1) and W52 (0.5 ± 1.0). Moreover, a sub-analysis showed that the probability of achieving ppPASI50 at W4 increased in case of nail psoriasis (p < 0.05) and decreased in bio-experienced patients (p < 0.001). Similarly, the probability of achieving ppPASI75 at W4 decreased in the case of prior biologic exposure (p < 0.05). Finally, patients with nail psoriasis showed a higher probability of reaching ppPASI75 at W16 (p < 0.05), whereas patients previously treated with systemic therapies for psoriasis reported a reduced probability of ppPASI75 achievement at this time point (p < 0.05)., Conclusion: Tildrakizumab was shown to be a fast and effective treatment for patients with PPp, being able to achieve significant results already after only 4 weeks of treatment. Moreover, the identification of potential clinical factors predictive of response may improve the selection of the best treatment in patients with PPp., Competing Interests: Declarations. Conflict of Interest: A. Campanati has served as consultant/advisor, received speaker honoraria and/or grants, and/or is investigator Abbvie, Galderma, Celgene, Janssen-Cilag, Leo-pharma, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, UCB, Almirall, Sanofi-Aventis, Boehringer-Ingelheim, Bristol Myers Squibb, Incyte; M Burlando has acted as speaker or advisory board member for Abbvie, Amgen, Leo-pharma, Eli Lilly, Novartis, UCB, Almirall; E. Cozzani has acted as speaker or advisory board member for Abbvie, Amgen, Leo-pharma, Eli Lilly, Novartis, UCB, Almirall; K. Hansel has acted as investigator and speaker for Abbvie, Almirall, Amgen, Novartis, and Sanofi; L. Stingeni has acted as investigator and speaker for Abbvie, Almirall, Amgen, Leo Pharma, Lilly, Novartis, Pfizer, and Sanofi; L. Bianchi has acted as speaker or advisory board member for Abbvie, Leo-Pharma, Eli Lilly, Novartis, Pfizer, UCB, Almirall, Sanofi-Aventis, Biogen, Bristol, Boehringer, Johnson & Johnson; M. Galluzzo acted as a speaker and/or consultant for AbbVie, Almirall, Eli-Lilly, Johnson & Johnson, LeoPharma, Novartis, and Sanofi; he has participated in clinical trials for AbbVie, Almirall, Boehringer-Ingelheim, Eli-Lilly, Incyte, Johnson & Johnson, Leo Pharma, Novartis and Sanofi.; M. Esposito has served as consultant/speaker from Abbvie, Amgen, Eli Lilly, Janssen, Leo Pharma, Novartis, UCB, Sanofi/Regeneron; MC Fargnoli has served as consultant/advisor, received speaker honoraria and/or grants, and/or is investigator for AMGEN, Almirall, Abbvie, Boehringer-Ingelheim, BMS, Galderma, Kyowa Kyrin, Incyte, LEO Pharma, Pierre Fabre, UCB, Lilly, Pfizer, Janssen, MSD, Novartis, Sanofi, Regeneron, Sun Pharma, Takeda; M. Megna has acted as a speaker or consultant for Abbvie, Amgen, Almirall, BMS, Boehringer, Leo-pharma, Eli Lilly, Janssen, Novartis, UCB; A. Balato has acted as speaker or advisory board member for Abbvie, Amgen, Almirall, BMS, Boehringer, Leo-pharma, Eli Lilly, Novartis, Pfizer, UCB, Sanofi. Federico Diotallevi, Pietro Quaglino, Luca Mastorino, Claudio Feliciani, Lucia Gallo, Agostina Legori, Giuseppe Argenziano, Federico Bardazzi, Paolo Gisondi, Francesco Bellinato, Tommaso Bianchelli, Giovanni Marco D’Agostino, Giulia Matacchione have no conflict of interest to declare. Anna Campanati is an Editorial Board member Dermatology and Therapy. Anna Campanati was not involved in the selection of peer reviewers for the manuscript or any of the subsequent editorial decisions. All authors read and approved the final version of the manuscript. Ethics Approval: The patients in this manuscript have given written informed consent to publication of their case details. IRB approval was waived, the study was conducted respecting the Declaration of Helsinki, and all patients signed an informed consent before starting the study., (© 2025. The Author(s).)

Background: Guselkumab has been shown to be safe and effective for the treatment of psoriasis in numerous randomized clinical trials and real-life studies. Real life data on treatment up to 4 years are lacking., Objectives: The present study aims to estimate the drug survival DS, effectiveness, and safety of guselkumab over a period of 208 weeks (w)., Methods: We included all consecutive patients with psoriasis or psoriatic arthritis receiving at least 1 dose of guselkumab. Effectiveness was evaluated according to the achievement of PASI100, 90 and <=3. DS was evaluated according to Kaplan-Meyer curve., Results: In atotal of 202 patients theeanPASI decreased from 10.88 (SD 5.76) at baseline to 0.48 at 208w. PASI100 showed an increasing response, the outcome was achieved in 30%, and 64.71% of patients at 16W, and 208W, respectively. For PASI90 and<=3 we found a similar trend. 208w of treatment, the estimated DS was 68.5% on observed cases. Being Super Responders (SRs) according to our (p=0.005) and the GUIDE definition (p<0.001), along with cardiovascular comorbidities reduced the risk of drug interruption. In our population none of the baseline characteristics showed a clear impact on the effectiveness of guselkumab. Considering both SR definitions, in our cohort being a SRs is associated with better response in the long-term when considering PASI100 and 90 in both linear and multivariate analysis., Conclusions: Our study confirms the good effectiveness and favorable safety profile of guselkumab in a real-world setting up to four years., (© The Author(s) 2025. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Atopic dermatitis (AD) is an inflammatory skin disease. The monoclonal antibody dupilumab can provide a rapid response with achievement of stable clinical disease. This study aimed to confirm the effectiveness of a televisit approach for patients with AD and treated with dupilumab., Methods: Demographic data and characteristics at baseline including mean EASI, mean NRSp, mean DLQI, and mean NRSds were retrospectively assessed and subsequently collected at up to 48 weeks, last visit in attendance, and up to the fourth televisit. The mean reduction of the above scores, and achievement at each time point of EASI≤7, EASI 75, EASI 90, DLQI 0/1, and NRSp≤4 were considered as endpoints., Results: Twelve patients underwent at least 1 televisit. The mean follow-up on dupilumab before switching to a televisit was 28.5 months. The mean EASI at the last face-to-face visit was 0.75 and remained stable at subsequent televisit visits. All patients achieved EASI≤7 as early as week 16 which was during the televisits. A similar trend was seen for EASI 75. Only 1 patient discontinued the televisits after 2 visits, preferring to return in person., Conclusions: In our case series of remotely-followed patients, clinical and patient-reported outcomes remained stable.

Background: Inverse psoriasis (IP) is a variant of plaque psoriasis involving flexor surfaces. A clear definition of IP is still lacking. Therapy is based on topical and systemic treatments, including classic systemic drugs and biologic agents, but a well-defined therapeutic strategy is absent., Materials and Methods: This retrospective study investigated the general characteristics of patients with IP or vulgar psoriasis and compared the effectiveness of anti-interleukin-17 or anti-interleukin-23 agents in the same groups. Second, treatment effectiveness and the demographic characteristics of IP patients treated with IL-23 and IL-17 inhibitors were also compared. IP patients were included if they had specific psoriatic involvement of the axillary, inguinal, or submammary lines, breast folds, antecubital and popliteal pits, intergluteal fold, and perianal area. Patients with vulgar plaque psoriasis and concomitant intertriginous involvement were included in the vulgar psoriasis cohort., Results: Patients with IP were prevalently female and treated with IL-17 inhibitors compared to those with vulgar psoriasis. They also had a greater risk of drug discontinuation and subsequent therapeutical switch (32.1% vs. 18.1%, P = 0.002). At later time points, those with IP showed progressively slower achievement of PASI100 and 90 compared to the cohort with vulgar psoriasis. In the IP cohort, there was greater joint involvement in patients treated with an anti-IL-17 agent (P = 0.011), who also had a lower median age of onset (P = 0.011) compared to patients treated with an anti-IL-23 agent. Patients with IP treated with an anti-IL-23 agent initiated with a lower mean PASI and showed a slower response than patients on an anti-IL-17 agent. At later time points, progressively greater effectiveness of IL-23 inhibitors was observed compared to IL-17 inhibitors., Conclusions: Patients with IP responded less to biologic agents than those with vulgar psoriasis. In the IP cohort, IL-17 inhibitors had a faster onset than IL-23 inhibitors, but long-term anti-IL-23 agents seem to be associated with better outcomes., (© 2024 the International Society of Dermatology.)

Background: De-escalation strategies have become increasingly used in the treatment of atopic Dermatitis® (AD) patients with dupilumab. Dose spacing (DS) refers to dose reduction by dosage elongation strategies from 2 to 8 weeks between dupilumab injections, in patients with stable response to treatment or affected by numerous adverse events. Objectives: Investigate safety and clinical effectiveness of DS strategy in AD patients treated with dupilumab. Methods: A retrospective cohort study was conducted on AD patients aged ≥18 years treated with dupilumab undergoing DS. Pre-post analyses were conducted on this cohort, termed cohort A, between effectiveness outcomes at baseline, at 16 weeks of treatment, at the index date identified as the mean follow-up time between dupilumab initiation and DS, and at subsequent two follow-up visits: T1 and T2. Based on the index date, a cohort B of AD patients on dupilumab treatment not experiencing DS was then compared with cohort A for the same outcomes at the same time points. Results: Seventy-three out of 452 patients treated with dupilumab underwent DS. The mean time since treatment initiation was 28.6 months. Mean Eczema Area Severity Index (EASI) from the index date remained stable until the second follow-up visit (T2) 0.2-0.8 with no significant pre-post differences ( P > 0.05). Similar considerations can be made for mean number rating scale worst pruritus (NRSp), numerical rating scale disturbs of sleeping/sleeping disturb (NRSsd), mean Dermatology Life Quality Index (DLQI), and EASI Head and Neck. Attainment of relative outcomes remained stable for EASI75, 90, ≤ 7, DLQI ≤ 5, and NRSp ≤ 4. When compared with cohort B, no clinically significant differences were observed in mean reductions in all outcomes analyzed. Conclusions: DS in our study appears to be an effective and safe strategy in treating patients with severe AD after the initial therapeutic response.

Background/Objectives: Patients with treated solid tumors (TST) are a highly heterogeneous and difficult-to-treat population due to the risk of disease progression/recurrence or infection. Methods: We conducted an observational, retrospective, single-center study at the Dermatology Clinic of Turin with a focus on the special population of cancer patients with psoriasis treated with biologics. Results: As of July 2023, 52 psoriatic patients with a prior/concomitant history of malignancy had taken biologic drugs. The median age was 67 years, and the median age of cancer onset was 55 years. The most common tumors were gastrointestinal cancer and melanoma. After the tumor diagnosis, 61% received an anti-IL17 drug; 37 patients continued the initiated biologic therapy, while 12 switched drugs due to secondary inefficacy. The estimated biologic DS was 55.6% at 50 months. Evidence suggests that IL-17 is a key pathogenic factor involved in tumorigenesis, resulting in a lower risk of malignancies in subjects managed with IL-17 inhibitors. Similarly, IL-23 plays a role in suppressing innate immunity and promoting tumor and metastases development. This is a consistent real-life case series that support the use of biologic drugs in patients with TST. Conclusions : IL-23 and IL-17 inhibitors, being immunomodulators rather than immunosuppressants, may be a safe option for patients in an active oncological setting and for immune-correlated adverse events.

Background: Psoriasis (PSO) involves about 1-3% of the population, and around 75% of women develop PSO before the age of 40. Official guidelines on the treatment of woman with anti-IL17 and anti-IL23 during this potential childbearing time are not currently available. Objective: To investigate the effectiveness and safety of biologic treatments in women of childbearing age. Methods: At the Dermatology Clinic of the University of Turin, Italy, 172 women aged 20-55 years underwent IL-17 and IL-23 inhibitor therapy for moderate-severe PSO and were followed up to 52 weeks in a real-life, retrospective, single-center study. Results: Overall, 40% of patients achieved PASI 100 at week 16, and 72% at week 52. A similar trend was observed for PASI 90 and PASI < 3 with almost 80% and 90% of patients achieving the target at 52 weeks. As for PASI 100, a statistically significant difference ( p = 0.004) was found at 16 weeks, with 23.84% of patients achieving PASI 100, with IL-17 and 15.70% with the IL-23 inhibitor. No statistically significant differences were found at 28 and 52 weeks. No statistically significant differences in PASIs at any time points were recorded across the different biologic agents. Forty-six patients discontinued treatment. The most reported side effects were headache, nausea, asthenia, injection site pain, and rhinitis. Conclusions: This study showed that biologic drugs are effective and safe in women of childbearing age, with negligible side effects.

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., (© 2024 European Academy of Dermatology and Venereology.)

Background: Alcohol abuse is correlated with the onset and worsening of psoriasis, but its effects, as for smoking, on biological therapies are still poorly investigated., Materials and Methods: This study aimed to determine the prevalence of alcohol abuse and other discretionary habits (such as smoking and sedentary lifestyle) in patients with psoriasis treated with topicals, conventional systemic and biologic therapies. The second objective is to investigate the impact of discretionary habits, focusing on alcohol abuse, on the response to biological therapy. To identify alcohol dependence, the CAGE questionnaire was distributed among patients of our clinic., Results: 305 patients were included with 18% at high risk of alcohol abuse. Clinically, guttate psoriasis and psoriatic arthritis were more common in patients at higher risk of alcohol abuse. Furthermore, patients with an alcohol problem who started biological therapy reported a higher PASI than those who drank less. None of the considered variables seemed to correlate with discontinuation of medication or with lower achievement of the analyzed outcomes (PASI100, PASI90, and PASI≤3). There was a stronger association between alcohol dependence and patients receiving conventional therapy than with patients receiving biologics., Conclusions: The efficacy of biologicals did not seem to be impacted by alcohol consumption, smoking, or sedentary lifestyle., (© 2024 The Author(s). Journal der Deutschen Dermatologischen Gesellschaft published by Wiley‐VCH GmbH on behalf of Deutsche Dermatologische Gesellschaft.)

Background: There are currently limited data on dupilumab drug survival (DS), especially on factors possibly associated with drug discontinuation., Materials and Methods: The primary endpoint of this study is to evaluate the parameters that may determine drug discontinuation and the predictive factors associated with dupilumab DS. We considered as independent associated factors: childhood onset of disease, gender, age of onset of AD, age of initiation of dupilumab, previous use of cyclosporine, initial mean EASI, atopic family history, and predisposition to allergic conjunctivitis., Results: On 413 patients DS was 94.5% at 1 year, 89.5% at 2 years, and 83.7% at 3 years, and after a mean follow-up of 40.5 months (±1.6) 53 patients had discontinued the drug permanently (12.8%). Univariate analysis showed that the only factor associated with a reduction in drug survival was a predisposition to allergic conjunctivitis (p 0.009). At multivariate Cox regression, male sex (HR, 2.34; 95% CI, 1.14-4.78; p 0.02) and predisposition to allergic conjunctivitis (HR, 2.61; 95% CI, 1.37-5.00; p 0.004) were associated with lower DS of dupilumab., Conclusion: Male gender and predisposition to allergic conjunctivitis are negative predictors for maintenance of response to treatment with dupilumab and consequently associated with lower DS rates.

Introduction: the selective IL-17 inhibitor secukinumab has demonstrated efficacy and safety in the treatment of moderate-severe psoriasis in recent years., Objective: evaluate effectiveness and drug survival (DS) of secukinumab in patients with psoriasis for up to 5 years., Methods: This is a retrospective study on a monocentric cohort of patients with psoriasis on secukinumab evaluating the achievement of PASI100, PASI90, and PASI ≤ 3 and DS analysis up to 260 weeks. DS multivariate analysis was carried out considering sex, age, age of onset of the disease, obesity, cardiovascular comorbidities, diabetes, involvement of difficult-to-treat sites, psoriatic arthritis, treatment-naïve status, and mean baseline PASI., Results: At baseline, we evaluated 255 patients on secukinumab. PASI100 was reached by 41.7% and 70.6% of patients at weeks 16 and 260, respectively. PASI90 showed a similar trend with 46.5% of patients achieving it at week 16 and 88.2% at week 260. Non-obese patients showed a faster response than patients with obesity in achieving PASI100, PASI90, and PASI ≤ 3, with significant differences at 28 weeks [55% vs. 40% ( p = 0.033), 64% vs. 49% ( p = 0.038), and 76% vs. 62% ( p = 0.036), respectively]. The estimated DS for secukinumab was 84.3% at 12 and 48% at 60 months. Obesity and smoking habits were associated with a higher risk of discontinuation in multivariate models (HR 1.6 CI 1.05-2.45, p = 0.028; HR 1.48 CI 1.01-2.17, p = 0.043, respectively)., Conclusions: Secukinumab showed effectiveness for up to 5 years of treatment, with a high DS and achievement of PASI100, PASI90, and PASI < 3 at these time points. Only obesity reduced the response and maintenance of DS.

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., (© 2024 the International Society of Dermatology.)

Competing Interests: Conflicts of interest None disclosed.

Introduction: Patients with psoriasis who have failed multiple biologic drugs have been defined as "multi-failure," although there are no clear data on the characteristics, comorbidities, and best treatment strategies for this population. Nowadays, given the next generation and the number of biologics available, patients are considered multi-failure when ≥4 biologics fail to achieve a good response., Methods: Demographic characteristics and efficacy of anti-interleukin drugs in multi-failure patients were compared to a cohort of general psoriatic patients treated with IL-23 or IL-17 inhibitors., Results: In total 97 multi-failure patients (≥4 lines of biologics) were compared with 1,057 patients in the general cohort. The current drugs in the multi-failure group were risankizumab (34), ixekizumab (23), guselkumab (21), brodalumab (7), tildrakizumab (5), ustekinumab (4), secukinumab (2), and certolizumab pegol (1). A significant difference was found in the multi-failure cohort for age of psoriasis onset (mean 29.7 vs. 35.1, P < 0.001), concurrent psoriatic arthritis (45.4 vs. 26.9%, P < 0.001), diabetes mellitus (30.9 vs. 10.9%, P < 0.001), and cardiovascular comorbidity (54.6 vs. 39.8%, P = 0.005). In multi-failure patients, current biological therapy showed a good initial response (PASI 90 and 100 of 41.24 and 27.84%, respectively, at 16 weeks); the response tended to decline after 40 weeks. Anti-IL-17 agents showed clinical superiority over IL-23 agents in terms of achieving PASI90 at 28 weeks (P < 0.001) and 40 weeks (P = 0.007), after which they reached a plateau. In contrast, IL-23 agents showed a slower but progressive improvement that was maintained for up to 52 weeks. A similar trend was also seen for PASI100 (28 weeks P = 0.032; 40 weeks P = 0.121)., Conclusions: The multi-failure patient is characterized by many comorbidities and longstanding inflammatory disease that frequently precedes the introduction of systemic biologic therapy. Further studies are needed to identify more specific criteria that could be applied as a guideline by clinicians., (© 2024 The Authors. International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

Purpose: The aim of this study was to evaluate the variation of dry eye disease (DED) prevalence in patients with atopic dermatitis (AD) treated with dupilumab., Methods: This prospective case-control study included consecutive patients with moderate-to-severe AD scheduled for dupilumab between May and December 2021 and healthy subjects. DED prevalence, the Ocular Surface Disease Index, tear film breakup time test, osmolarity, Oxford staining score, and Schirmer test results were collected at baseline, 1 month, and 6 months after dupilumab therapy. The Eczema Area and Severity Index was assessed at baseline. Ocular side effects and discontinuation of dupilumab were also recorded., Results: Seventy-two eyes from 36 patients with AD treated with dupilumab and 36 healthy controls were included. Prevalence of DED increased from 16.7% at baseline to 33.3% at 6 months in the dupilumab group ( P = 0.001), whereas it remained unchanged in the control group ( P = 0.110). At 6 months, the Ocular Surface Disease Index and Oxford score increased (from 8.5 ± 9.8 to 11.0 ± 13.0, P = 0.068, and from 0.1 ± 0.5 to 0.3 ± 0.6, P = 0.050, respectively), the tear film breakup time test and Schirmer test results decreased (from 7.8 ± 2.6 s to 7.1 ± 2.7 s, P < 0.001, and from 15.4 ± 9.6 mm to 13.2 ± 7.9 mm, P = 0.036, respectively) in the dupilumab group, whereas they remained stable in the control group ( P > 0.05). Osmolarity was unchanged (dupilumab P = 0.987 and controls P = 0.073). At 6 months after dupilumab therapy, 42% of patients had conjunctivitis, 36% blepharitis, and 2.8% keratitis. No severe side effects were reported, and none of the patients discontinued dupilumab. No association between Eczema Area and Severity Index and DED prevalence was shown., Conclusions: DED prevalence increased in patients with AD treated with dupilumab at 6 months. However, no severe ocular side effects were found and no patient discontinued therapy., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Biologics targeting IL-23 and IL-17 show efficacy and safety in the treatment of moderate-to-severe psoriasis., Objective: To investigate drug survival in patients with psoriasis treated with biologics., Patients and Methods: We performed a comparative evaluation of the achievement of PASI 90 and PASI ≤ 3 at 16, 28, and 52 weeks along with a DS (drug survival) analysis with IL-17 and IL-23 inhibitors brodalumab, ixekizumab, secukinumab, risankizumab, tildrakizumab, and guselkumab on 1,057 patients., Results: IL-17 inhibitors showed a faster achievement of PASI 90 and PASI ≤ 3 with significant superiority over IL-23 inhibitors at week 16 (p < 0.001; 56% vs. 42% and 70% vs. 59%, respectively). A difference was shown in favor of IL-23 inhibitors regarding DS (p < 0.001), which was 88% at 24 months vs. 75% for IL-17 inhibitors. In multivariate analysis, IL-23 inhibitors (HR 0.54 CI 0.37-0.78, p = 0.001), and male sex (HR 0.57 CI 0.42-0.76, p < 0.001) were all associated with a lower probability of drug interruption. Risankizumab (HR 0.42 CI 0.26-0.69, p = 0.001), guselkumab (HR 0.49 CI 0.24-0.99, p = 0.046), and male sex (HR 0.57 CI 0.43-0.77, p < 0.001) were associated with a lower probability of drug interruption than secukinumab., Conclusions: IL-23 inhibitors showed the best performance on DS. Overall, the most effective class was IL-17 inhibitors considering the short-term effectiveness, but long-term effectiveness is in favor of anti-IL-23., (© 2023 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Rosai-Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy (SHML), is a rare subtype of reactive histiocytosis which is seldom associated with Hodgkin's and non-Hodgkin's lymphomas. To date, the coexistence in the same patient of extra nodal SHML and primary cutaneous B-cell lymphoma (PCBCL) has been reported in the literature, as metachronous diagnosis in the anatomical area of the original PCBCL or synchronous occurrence in the same lesions. However, no data have been published as for synchronous occurrence of the two pathological entities in distinct anatomical sites. Herein, we report the first ever described synchronous occurrence of PCBCL and SHML, detected in distinct lesions, affecting the same patient. The complete resolution of the patient's PCBCL after rituximab treatment and the concomitant regression of SHML suggest that this clinically benign reactive histiocytic proliferation, potentially triggered by the lymphoma microenvironment itself, may take place not only in the site of the PCBCL lesion, but also in other distant areas not directly affected by the primary cutaneous lymphoma., (© 2023 The Authors. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.)

Background: Interleukin 23 (IL-23) inhibitors, such as guselkumab, risankziumab, and tildrakizumab, have proved to be highly effective and safe for psoriasis treatment either in bio-naïve or bio-experienced patients. A substantial proportion of patients show a primary or secondary inefficacy to IL-17 inhibitors and can benefit from an alternative line of treatment, like IL-23 inhibitors. To date, no sufficient data are available on the effectiveness of IL-23 inhibitors after an anti-IL-17 agent., Methods: Our study includes 48 patients with moderate to severe psoriasis undergoing a switch from IL-17 to IL-23 inhibitors. This trial is registered with SS&#95;DERMO&#95;20., Results: The mean PASI (Psoriasis Area Severity Index) decreases from 11.6 to 3.3 at week 16, with responses maintained at weeks 28 and 52 (2 and 1.4, respectively), and a PASI100 achievement in more than 24% of patients at 16 weeks and 61.9 at 48 weeks, with no occurrence of serious adverse events. However, almost one in six patients interrupted the IL-23 inhibitors mainly due to primary ineffectivenss., Conclusions: Our data support the evidence that an interclass switch among IL-17 inhibitors is a safe and effective therapeutic option for these patients.

Vitiligo, the most prevalent skin depigmenting disease, is characterized by the selective loss of melanocytes, impacting patients' quality of life significantly. This autoimmune disorder progresses through a complex interplay of genetic and non-genetic factors, posing challenges in comprehending its pathogenesis and devising effective treatment strategies for achieving remission. Existing conventional therapeutic approaches, such as topical and oral corticosteroids, calcineurin inhibitors, and phototherapy, lack specificity, offer modest efficacy, and may entail potential adverse effects. Consequently, there is a pressing need for a more nuanced understanding of vitiligo's pathogenesis to pave the way for targeted therapeutic innovations. This review aims to provide a comprehensive overview of recent developments and findings concerning Januse Kinase (JAK) inhibitors and biologics tested in vitiligo patients. JAK inhibitors have exhibited promising results, showcasing both efficacy and tolerability. In contrast, the outcomes of biologics treatment have been more varied. However, to establish a clearer understanding of which specific pathways to target for a more effective approach to vitiligo, additional in vitro studies and extensive clinical research involving a larger population are imperative.