Assessing a measure for Quality of Life in patients with severe Alopecia Areata: a multicentric Italian study.

Objective: The prevalence of anxiety and depression in patients diagnosed with Alopecia Areata (AA) is very high and this significant burden of psychological symptoms threatens the Health-Related Quality of Life (HRQoL) of affected patients. Indeed, AA often does not produce significant physical symptoms, but it nonetheless disrupts many areas of mental health. Clinical assessment of disease severity may not reliably predict patient's HRQoL, nor may it predict the patient's perception of illness. For this reason, considerable effort has been made to apply and develop measures that consider patient's perception and assess the HRQoL of individuals affected by AA. The aim of this multicentric study was to provide the Italian version of the Skindex-16AA and to evaluate its psychometric properties in a clinical sample of consecutive patients with moderate-to-severe AA. Methods: This is a longitudinal, multicenter, observational study. Patients returned for follow-up visits at 4-, 12-, and 24-weeks. The analyses of the current work aimed to confirm the factorial structure of the Skindex-16AA. In the case of non-fit, an alternative structure for the model was proposed, using an Exploratory Graph Analysis and the Bayesian approach. Results: The sample was composed of 106 patients with AA. Alopecia Universalis was the most frequently diagnosed type of alopecia at all time points. The analyses on the Skindex-16AA revealed that a two-factor structure with eight items fit the data best (Bayesian Posterior Predictive Checking using 95% Confidence Interval for the Difference Between the Observed and the Replicated Chi-Square values = -6.246/56.395, Posterior Predictive P-value = 0.06), and reported satisfactory psychometric properties (i.e., internal consistency and convergent validity). Conclusion: The Skindex-8AA demonstrated optimal psychometric properties (i.e., convergent and construct validity, and test-retest reliability) measured in a sample of patients with AA, that may suggest that it is an appropriate tool to measure the HRQoL in AA patients. However, further studies are needed in order to confirm and tested other psychometric features of this tool.

Effectiveness of Ixekizumab in Elderly Patients for the Treatment of Moderate-to-Severe Psoriasis: Results From a Multicenter, Retrospective Real-Life Study in the Lazio Region.

INTRODUCTION: This was an observational, retrospective, multicenter study, enrolling elderly patients (>65 years old) treated with ixekizumab with a diagnosis of psoriasis (PsO) and/or psoriatic arthritis (PsA) during the period 2020 to 2023. OBJECTIVES: Efficacy of ixekizumab in elderly patients in the treatment of moderate to severe psoriasis. METHODS: We included 73 patients with psoriasis (32.9%), psoriatic arthritis (1.4%) and both of them (PsO-PsA 65.8%), attending the outpatient clinics of seven Italian referral center for psoriasis in Lazio region: Policlinico Umberto I Università Roma La Sapienza, Sant'Andrea Università di Roma La Sapienza, Polo Pontino Università Roma La Sapienza, Fondazione Policlinico Universitario A. Gemelli, Università Campus Biomedico Roma, Istituto Dermopatico dell'Immacolata - IDI and Policlinico Tor Vergata. We collected data related to the characteristics of the patients (age, sex, body mass index) and of the disease (age at onset, duration of psoriasis, previous treatments). The severity of psoriasis was measured with the Psoriasis Area and Severity Index (PASI) score at baseline and after 16, 24, 52, 104 and 156 weeks of treatment. RESULTS: PASI90 was achieved by all the patients in week 16 and remained stable until the end of the study. PASI100 has been achieved by 55.1% of patients at weeks 16 and by 81.3% at week 104. A statistically significant difference has been showed between baseline and all the other time points (P < 0.0001) for PASI score. A similar trend was observed for Visual Analogue Scale score and Dermatology Life Quality Index score. CONCLUSIONS: Ixekizumab was effective and with a good safety profile in psoriatic patients over 65 years. No significant adverse events were reported.

Anti-IL-17 monoclonal antibodies and bullous pemphigoid: treatment or causal agents? A case series and review of the literature.

Bullous pemphigoid (BP) is an autoimmune bullous disease, typically affecting the elderly, characterized by the production of autoantibodies directed against structural components of the dermal-epidermal junction. An association between BP and psoriasis has been described several times, but the mechanisms underlying this association have yet to be clearly defined. The pathophysiological mechanism underlying psoriasis may be implicated in the pathogenesis of BP, as psoriasis precedes BP in most cases; in particular, a promoting role has been hypothesized by biologic therapies, which may induce a switch from a T helper 1 (TH1)/TH17-dominant cytokine milieu, typical of patients with psoriasis, to a TH2-dominant one, typical of patients with BP. IL-17 inhibitors, in particular, have also been successfully used to treat BP in patients with psoriasis. The use of these drugs in these patients has been based on in vitro studies. However, cases of new-onset BP or relapses of BP already diagnosed in patients with psoriasis treated with biologic drugs have also been reported, and they occurred mainly in patients on anti-TNF drugs, yet very few cases with anti-IL-17A drugs have been described. We hereby describe two cases of new-onset BP in two patients treated with anti-IL-17 drugs for psoriasis.

Long-Term Persistence Rate of Secukinumab in Psoriatic Patients: A Six-Year Multicenter, Real-World Experience, Retrospective Study.

Background: Psoriatic disease, a chronic immune-mediated systemic inflammatory condition, significantly impairs patients' quality of life. The advent of highly targeted biological therapies has transformed treatment strategies, emphasizing the importance of selecting the most effective and cost-efficient option. Secukinumab, an IL-17A inhibitor, has demonstrated efficacy and safety in treating moderate-to-severe plaque psoriasis (PsO). However, long-term real-world data on its effectiveness and persistence rate are limited. Methods: This retrospective study, conducted across eight Italian dermatology centers, aimed to evaluate the 6-year persistence rate and effectiveness of secukinumab in patients with PsO. Additionally, the study investigated the onset of psoriatic arthritis during treatment. Results: Overall, 166 adult patients were analyzed. Their median age was 53.9 years. The mean BMI was 26.5. Of the 166 patients, 64 were bio-experienced while 102 were bio-naïve. A progressive reduction in PsO severity measured by PASI scores over 6 years of treatment was revealed: the PASI score decreased from a baseline value of 18.1 (±9.1) to 0.7 (±1.6) after 6 years of follow-up. Adverse events, including mucocutaneous fungal infections and cardiovascular disturbances, were reported in 19.9% of patients. The persistence rate was 86.8% at 24 months, decreasing to 66.4% at 72 months. Psoriatic arthritis onset during treatment was observed in 15 (9.0%) of patients. Conclusions: This study highlights the sustained effectiveness and favorable safety profile of secukinumab over 6 years, providing valuable real-world evidence. Understanding the long-term persistence rate and predictors of discontinuation could help clinicians optimize treatment decisions and improve patient outcomes in PsO management. We found that the absence of scalp PsO, no involvement of the genital area and normal weight were the best factors of persistence in secukinumab treatment in the long term.

Short-term efficacy of tildrakizumab on difficult-to-treat areas: a real-world experience.

BACKGROUND: Novel biologics targeting the IL23/T-17 axis, such as tildrakizumab, have been developed to treat psoriasis. There is limited evidence on the use of tildrakizumab for the treatment of psoriasis in difficult-to-treat areas. OBJECTIVE: Our aim was to evaluate the short-term efficacy and safety of tildrakizumab in patients with moderate-to-severe psoriasis and with the involvement of difficult-to-treat areas. METHODS: A multicentric retrospective study was conducted on patients who initiated tildrakizumab between July 2022 and July 2023. Psoriasis Area and Severity Index (PASI), Psoriasis Scalp Severity Index (PSSI), Palmoplantar Psoriasis Area and Severity Index (ppPASI), and Nail Psoriasis Severity Index (NAPSI) were measured at baseline and after 16 weeks. The percentages of achieving a PASI75, PASI90, or PASI100 response were assessed. Dermatology Life Quality Index (DLQI) and Itch Visual Analog Scale (VAS) were measured simultaneously. Data about potential safety issues and adverse events were collected. RESULTS: A total of 76 patients were included, and 59 (77.6%) were affected by psoriasis localized to the scalp (n = 32), palmoplantar locations (n = 13), or nails (n = 14). The mean PASI score decreased from 16.5 ± 9.8 at baseline to 1.9 ± 1.6 after 16 weeks. Tildrakizumab treatment resulted in the improvement of PSSI (19.9 ± 10.7 to 2.7 ± 4.2), ppPASI (15.4 ± 6.9 to 1.9 ± 2.3), and NAPSI (20.3 ± 16.9 to 7.6 ± 10.8) from baseline to 16 weeks, respectively. DLQI and Itch VAS also showed marked improvement. CONCLUSIONS: Tildrakizumab is a valuable option for treating difficult-to-treat psoriasis and pruritus, with rapid onset of action.

Evaluation of the Impact of Night Shift Work on Disease Severity in Psoriatic Patients: A Case-Control Study with Clinical, Hormonal, and Immunological Evaluation.

INTRODUCTION: Night shift work disrupts circadian rhythms and has been associated with immune system alterations and various health conditions. However, there is limited data regarding its impact on psoriasis. The aim of our study was to compare psoriasis severity and the hormonal and immunological profile in patients with a night shift work to those with a daytime occupation. METHODS: In this case-control study, we enrolled psoriatic patients aged >18 years engaged in night shift work and a control group of psoriatic patients with a daytime occupation. A further categorization was performed by the duration of night shift work: < or ≥7 days a month and < or ≥8 years. Disease severity was evaluated by PASI, BSA, and DLQI, and blood samples were taken to measure various hormonal and immunological markers. Univariable and multivariable analysis were performed to assess differences between the two groups. RESULTS: A total of 40 night shift workers were included, along with 36 patients in the control group. Patients who worked night shifts at least 7 days a month had significantly higher PASI scores (11.2 ± 6.6 vs. 8.5 ± 6.6; p = 0.04) and higher IL-8 serum (115.33 ± 463.65 pg/mL vs. 19.98 ± 29.78 pg/mL; p = 0.006) compared to patients who did not. Night shifts workers for at least 8 years had higher BMI (28.65 ± 4.56 vs. 25.32 ± 5.50, p = 0.010), and females had higher testosterone levels (0.46 ± 0.53 ng/mL vs. 0.23 ± 0.13 ng/mL; p = 0.055). CONCLUSION: Night shift might increase psoriasis severity and have an impact on chronic inflammation, obesity, and hormonal imbalances.

Italian National Registry of Alopecia Areata: an epidemiological study of 699 Italian patients.

BACKGROUND: Alopecia areata (AA) is an organ-specific autoimmune disease that affects the hair follicles of the scalp and the rest of the body causing hair loss. Due to the unpredictable course of AA and the different degrees of severity of hair loss, only a few well-designed clinical studies with a low number of patients are available. Also, there is no specific cure, but topical and systemic anti-inflammatory and immune system suppressant drugs are used for treatment. The need to create a global registry of AA, comparable and reproducible in all countries, has recently emerged. An Italian multicentric electronic registry is proposed as a model to facilitate and guide the recording of epidemiological and clinical data and to monitor the introduction of new therapies in patients with AA. METHODS: The aim of this study was to evaluate the epidemiological data of patients with AA by collecting detailed information on the course of the disease, associated diseases, concomitant and previous events, and the clinical response to traditional treatments. Estimate the impact on the quality of life of patients. RESULTS: The creation of the National Register of AA has proven to be a valid tool for recording, with a standardized approach, epidemiological data, the trend of AA, response to therapies and quality of life. CONCLUSIONS: AA is confirmed as a difficult hair disease to manage due to its unpredictable course and, in most cases, its chronic-relapsing course, capable of having a significant impact on the quality of life of patients.

Rapid response on facial psoriasis to bimekizumab: case series.

Psoriasis is a chronic inflammatory disease that can affect any part of the body but, when it appears in certain areas, like the face, it can have a very significant psychological impact. Biologics, in particular IL-17 and IL-23 drug inhibitors, have shown relevant clinical efficacy in the management of psoriatic lesions in difficult-to-treat areas. In post hoc analysis of phase III trials in plaque psoriasis, bimekizumab has shown safety and complete clearance of high-impact areas. However, these studies did not focus on the effect of bimekizumab on facial lesions. Therefore, this case series represents the first clinical real-life experience of rapid and successful management of facial psoriasis with bimekizumab in six patients.

Long-Term Effectiveness of Brodalumab for the Treatment of Moderate-To-Severe Psoriasis: A Real-Life Multicenter Study of Up to 3 Years in a Real-Life Italian Cohort.

INTRODUCTION: Data about the long-term effectiveness of brodalumab could be valuable in assessing patient adherence to treatment and improving psoriasis management. OBJECTIVE: The aim of our study was to evaluate the drug survival of brodalumab and identify any predictive factors for discontinuation. METHODS: A multicenter retrospective study was conducted in patients with moderate-to-severe psoriasis who were treated for up to 3 years. We extracted data from patient files, related to the characteristics of the patients and the disease. Drug survival analysis was descriptively analyzed using Kaplan-Meier survival curves. Univariable and multivariable analyses were performed to assess baseline patient characteristics that predicted clinical response. RESULTS: The study included 90 patients. Among them, 28 (31.1%) suspended brodalumab through the observation period. At weeks 52, 104 and 156 the median PASI score were 0.0 [0.0 - 0.8], 0.0 [0.0 - 1.0] and 0.0 [0.0 - 0.0], respectively. The estimated cumulative survival rates at weeks 52 and 104 were 86.32% and 78.09%, respectively. In the multivariable survival analysis, predictor factors for overall discontinuation included body mass index (BMI) (OR 1.10, 95% CI 1.03 - 1.18), baseline PASI (OR 1.06, 95% CI 1.02 - 1.10), and psoriatic arthritis (OR 5.05, 95% CI 0.89 - 13.50). CONCLUSIONS: Brodalumab has shown long-term effectiveness for up to 3 years. Considering baseline disease severity and patient characteristics could aid in optimizing the long-term management of psoriasis.

Infectious events in patients with alopecia areata treated with JAK inhibitors: low burden and minimal impact on persistence in treatment.

BACKGROUND: Alopecia areata (AA) is a non-scarring disorder characterized by hair loss that greatly affects patients' quality of life and has a chronic, recurring course. This disease is marked by an inflammatory process, mainly on an autoimmune basis primarily regulated by Janus kinase (JAK). RESEARCH DESIGN AND METHODS: We conducted a retrospective study evaluating the safety of JAKi in a real-world setting in 91 AA patients, with a specific focus on the assessment of infectious events. RESULTS: Overall, 34 infectious events were observed in 28 patients (30.8%), among them 17 patients (60.7%) suspended treatment with JAKi until the infection was clinically resolved. Only in one case the infectious event led to a permanent discontinuation of the treatment. The data we observed in the study are consistent with results reported in clinical trials. CONCLUSION: It can be stated that, during treatment with JAKi in AA patients, infectious events may occur, but in most cases these events are easily manageable and do not result in permanent discontinuation of the drug.

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.

Clinical, epidemiological, and therapeutic hallmarks of pyoderma gangrenosum: a case series of 35 patients.

BACKGROUND: Over the past few decades, advances in medical research and diagnostic tools have shed light on some aspects of pyoderma gangrenosum (PG). Nevertheless, the multifactorial etiology, pathogenesis, and optimal management strategies for PG need to be further investigated. To address these knowledge gaps and contribute to a better understanding of this complex dermatological disorder, we collected epidemiological, clinical, and therapeutic aspects of a case series of PG patients occurring in our department over the past 10 years. METHODS: We performed a single-centered, retrospective, observational study analyzing all cases with a diagnosis of PG observed at the Dermatology clinic of the Fondazione Policlinico A. Gemelli IRCCS Catholic University from January 1, 2013, to January 1, 2023. For each case, we retrieved demographic data, the presence of other skin and systemic conditions, and the histopathological and clinical characteristics of PG, such as clinical variant, number of lesions, disease localization, previous therapy, response to treatment, and occurrence of relapse. RESULTS: We included 35 patients, 22 females and 13 males with a mean age of 40.0 years. Twenty patients (57.1%) had multiple localizations of disease, and the most commonly involved site was the lower limbs (85.7%). The lesions were mainly associated with inflammatory bowel diseases (51.4%) and hidradenitis suppurativa (37.1%). Clinical resolution with complete re-epithelialization was achieved in 25 patients (71.4%) with an average time of 20.8 months. On average, patients who underwent therapy with biological drugs had better outcomes. CONCLUSIONS: PG is a severe, rare, and pleomorphic disease associated with a broad spectrum of conditions. Corticosteroids remain the primary first-line approach for severe forms, but using biological immunosuppressants is promising.

Bimekizumab for the Treatment of Plaque Psoriasis with Involvement of Genitalia: A 16-Week Multicenter Real-World Experience - IL PSO (Italian Landscape Psoriasis).

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.

Efficacy and safety of tildrakizumab in elderly patients: real-world multicenter study (ESTER - study).

Purpose of the article: Interleukin-23 inhibitors, such as tildrakizumab, have emerged as safe and effective options for the management of psoriasis. Yet their efficacy in elderly patients (aged 65 years or more), particularly in those with difficult-to-treat areas involvement, remains insufficiently explored. We conducted this real-life retrospective multicentric observational study to assess the effectiveness of tildrakizumab in elderly patients with moderate-to-severe psoriasis, with involvement of difficult-to-treat areas.Materials and methods: We enrolled forty-nine patients aged 65 years old or more (mean age 73.1 ± 6.0), all treated with tildrakizumab for at least 28 weeks. The effectiveness of tildrakizumab was assessed by Static Physician's Global Assessment of Genitalia (sPGA-G), fingernail-PGA (f-PGA), palmoplantar PGA (pp-PGA), scalp-specific PGA (sc-PGA), and Psoriasis Area and Severity Index (PASI) scores.Results: Significant improvements in PASI scores were observed within 28 weeks of treatment, with 77.5%, 60%, and 45.2% of patients achieving PASI75, PASI90, and PASI100, respectively. The mean PASI decreased significantly from baseline (13.6 ± 9.9) to 1.3 ± 1.7 at week 28. More than 90% of patients had clear sPGA-G and pp-PGA scores and over 70% had clear f-PGA and sc-PGA scores after 28 weeks.Conclusions: Our findings suggest that tildrakizumab could be a valuable option for the treatment of elderly patients, including those with difficult-to-treat areas involvement.

Drug survival of biologics and non-biologics in patients affected by palmoplantar psoriasis: a "real-world", mono-center experience.

BACKGROUND: Data on the treatment of palmoplantar psoriasis (PP) are very limited as these patients are often excluded from clinical trials. Moreover, this form of psoriasis is often resistant to treatment, making its clinical management complex. METHODS: Primary endpoint was to evaluate the clinical and demographic characteristics and the drug survival of both biological and non-biological drugs in a population affected by PP. Secondary endpoint was to highlight any differences between the hyperkeratotic and pustular variant. We analyzed data from 233 psoriasis patients with palmoplantar involvement, with or without chronic plaque psoriasis. We performed a drug-survival analysis with the aid of Kaplan-Meier survival and a multivariate analysis to highlight the influence of certain variables on treatment persistence using a Cox regression model. RESULTS: The drug-survival analysis revealed that biologic drugs compared to non-biologic drugs are associated with a higher persistence in treatment (59.73 vs. 43.56%); in particular, anti-IL23 drugs were found to be the drugs with the best drug-survival overall (67.94% of patients at 60 months are still on these drugs). Furthermore, our multivariate analysis shows that when compared with biological drugs, non-biological drugs are associated with an increased risk of treatment discontinuation (HR = 1.95 [95% CI: 1.41-2.68], P = 0.001). CONCLUSIONS: Our study confirms the difficulty of treating PP and shows that biologic drugs are associated with longer persistence in treatment than non-biologics in both PP's variants, not because of their higher effectiveness but because of their better safety profile.

Infectious adverse events in patients with atopic dermatitis treated with baricitinib.

Baricitinib is a JAK1-2 inhibitor recently approved in Europe and Japan for the treatment of moderate-to-severe atopic dermatitis in adult patients at doses of 2 and 4 mg daily. The aim of this article is to discuss the safety profile of baricitinib in atopic dermatitis using data from clinical trials and the supporting literature, with a focus on infectious adverse events. An integrated analysis of safety data from eight clinical trials described infections as the most frequent treatment-emergent adverse events, mainly of mild-to-moderate severity, notably upper respiratory tract infections and herpes simplex exacerbations. Real-world data are still limited and will contribute to precisely profile the patients that might benefit from this treatment.

Baricitinib is a drug taken by mouth, currently approved for the treatment of moderate-to-severe atopic dermatitis in adults who are candidates for systemic therapy, a medication that is designed to be absorbed into the bloodstream and work throughout the body. Baricitinib is available as 2- and 4-mg tablets and has been shown to improve the cutaneous manifestations, such as dry and cracked skin, redness and symptoms of atopic dermatitis, especially itchiness. Baricitinib is generally well tolerated. The most common adverse events that have emerged from clinical trials include headache, nausea and high cholesterol. Another reported side effect is an increased risk of infections, mainly of mild-to-moderate severity, especially upper respiratory tract infections such as nasopharyngitis (inflammation of the nose and throat) and reactivation of herpes zoster, a virus that causes a painful rash on one side of the body, and herpes simplex, which causes clustered blisters usually on the lips or genitals. There is still a lack of data from real-world experience, which will be important for the development of a more precise profile of patients who may benefit from this treatment.

The preclinical discovery and development of deucravacitinib for the treatment of psoriasis.

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease that most commonly presents as plaque psoriasis. The understanding of the pivotal pathogenetic role of the IL-23/IL-17 axis has dramatically changed the therapeutic approach to the disease. The identification of intracellular signaling pathways mediating IL-23 activity provided the rationale for targeting TYK2. AREAS COVERED: This review assesses the underlying rationale that led to development of deucravacitinib, a novel oral TYK2 inhibitor, as a therapeutic option for the treatment of moderate-to-severe psoriasis, primarily focusing on pre-clinical and early phase clinical studies. EXPERT OPINION: Innovative therapies used in patients with moderate-to-severe psoriasis include biologic agents and small molecules, which are associated with less adverse events than traditional systemic agents. Deucravacitinib, which selectively targets TYK2, has demonstrated to be effective in treating psoriasis, preserving a more favorable safety profile compared to other JAK inhibitors approved for the treatment of other immune diseases that block the ATP-binding site. Because of its oral administration, deucravacitinib represents an intriguing option in the therapeutic armamentarium of psoriasis, though the evaluation of long-term efficacy and safety is necessary to establish its place-in-therapy.