OPT-In; Optimized Patient Treatment Outcomes in Plaque Psoriasis: A 3-Year State-Transition Treatment-Sequencing Model in the Italian Setting.

INTRODUCTION: There are several treatment options for plaque psoriasis (PsO), but uncertainty remains around the optimal sequencing of treatments. The aims of this study were to investigate how adopting a best-treatment-first treatment sequence impacts patient outcomes and healthcare systems and to quantify the cost of treatment failure to the healthcare system. METHODS: A 3-year state-transition treatment-sequencing model which identifies all possible treatment sequences in PsO was adapted to the Italian healthcare setting. Treatments considered in the model are those with European Medicines Agency marketing authorization and reimbursement in Italy as of December 2022. Italian market share data (2019-2021) and list prices (2022) informed the current prescribed sequences; these sequences were compared against all possible sequences to determine opportunities for improvement. Both the national perspective in Italy as well as the local perspective from seven regions were considered. The cost of treatment failure was informed through a questionnaire circulated to Italian dermatologists. RESULTS: Overall, 1284 possible treatment sequences are possible when four lines of treatment are considered for patients with moderate-to-severe PsO in Italy. Within the estimated range of treatment failures across those sequences (0.97-2.56 per patient over 3 years), current prescribing behavior from the national perspective suggests patients will face 1.44 failures on average; this highlights the potential for improvement. For every treatment failure, the cost borne by the Italian National Healthcare Service (NHS) is €676.80. Overall, prescribing more optimized treatment sequences results in a 22.95% reduction in failures with a 2.27% increase in costs. The regional analyses found similar trends. CONCLUSIONS: Results suggest that selecting the most effective treatment sequences for incident patients provides the greatest opportunity to reduce treatment failures and maximize patient outcomes with a modest impact on costs. While regional variations exist, there is room for improvement across the board, which could translate to more efficient local healthcare systems.

Adalimumab in the management of psoriasis and psoriatic arthritis: Results from a Delphi investigation.

Background and Objectives: Psoriasis (PsO) and psoriatic arthritis (PsA) are often undertreated and require a multidisciplinary approach. In recent years, patent expiration has allowed the introduction of tumor necrosis factor inhibitor (anti-TNF) biosimilars, which have stimulated a significant increase in the use of biological therapies. This article reports the findings of a multidisciplinary approach to achieve a consensus on the use of adalimumab in patients with PsO or PsA. Methods: A voting panel of 36 Italian dermatologists and rheumatologists were chosen by eight Italian clinicians (the Board), to provide a consensus on the real-world management of PsO and PsA with adalimumab using the Delphi Method, comprising three survey rounds. Twelve statements were defined by the Board and submitted to the panel (rating scale 1-7). Results: Clinicians reached a wide consensus on the effectiveness (score 6-7: 67%) and long-term efficacy (6-7: 100%) of adalimumab in all clinical forms of PsO and PsA, including pediatric patients (6-7: 85%). Considering cost-effectiveness and safety, adalimumab is suggested as a first-line treatment in patients with enthesitis, predominant peripheral arthritis, axial involvement or associated inflammatory bowel disease (IBD) or uveitis. Adalimumab can be also considered after failure of etanercept (6-7: 94%). Conclusion: Results from this Delphi study clearly show an overall consensus on the use of adalimumab in the management of PsO and PsA, particularly as first-choice for specific subpopulations (uveitis, IBD, hidradenitis suppurativa). Considering the cost-effectiveness of biosimilars within Italy, adalimumab may represent an effective and safe first-line treatment for patients with moderate-to-severe PsO or PsA, and a valid choice for switching after failure.

Epidemiology, characteristics of disease and unmet needs of patients with generalized pustular psoriasis: a large Italian Delphi consensus.

INTRODUCTION: Generalized pustular psoriasis (GPP) is a rare and chronic, debilitating skin condition characterised, in its acute flare phase, by clinically severe and potentially life-threatening systemic manifestations. Data on GPP are still scanty, particularly in Europe and at a national level. To provide expert indications on several disease-related and patient-related aspects of GPP, with specific focus to the Italian context. METHODS: We conducted an iterative eDelphi study following the recommended criteria for reporting methods and results. After a thorough bibliographic review aimed to identify unknown or controversial issues in GPP, the following areas were investigated through a few specific questions/statements for each area: 1) disease epidemiology; 2) disease characteristics, with specific interest towards GPP flares; 3) diagnosis and diagnostic delay; 4) GPP treatment; 5) GPP patient journey and use of healthcare resources in Italy; 6) unmet needs and quality of life. An Executive Board of 9 principal investigators revised and approved the topics to be examined and overviewed the whole project. A total of 35 experts from different Italian areas, including 34 board-certified Italian dermatologists and one representative of patients' associations, took part in the study. RESULTS: A high agreement in responses from Italian experts emerged during two eDelphi iterations on - among several other aspects - GPP prevalence and incidence in Italy, use of European Rare and Severe Psoriasis Expert Network diagnostic criteria, flare frequency and duration, best diagnostic and care pathway, and main unmet needs of Italian patients. On the other hand, a broad spectrum of treatments (of different drug classes) was reported both in the acute and chronic phases of GPP, and no consensus on the issue was thus achieved. CONCLUSIONS: Consensus findings from this Delphi study of GPP experts may be useful to fill gaps of knowledge and improve awareness of this rare disease, as well as to help clinical and public health management of GPP in Italy.

Effects on Lipid Profile after One Year of Apremilast Therapy in Patients with Psoriasis: A Monocentric Experience.

Apremilast, a phosphodiesterase-4 inhibitor, has shown promise to have a potential beneficial metabolic effect. We conducted a single-centre retrospective study on adult patients with moderate-to-severe psoriasis who underwent apremilast treatment over at least 12 and 52 weeks, respectively. Baseline characteristics, weight, lipid profile, and fasting glucose levels were collected at baseline and at 12, 24, and 52 weeks. Furthermore, we conducted a narrative review of the current scientific knowledge on the metabolic effects of apremilast in patients with psoriasis and psoriatic arthritis. We observed a significant reduction in average weight and body mass index (BMI) in patients treated with apremilast in both the initial and the subgroup analysis, a significant reduction in triglycerides levels at 24 and 52 weeks, and a significant increase in high-density lipoprotein (HDL) levels at 52 weeks, whereas there were no significant changes in total cholesterol or low-density lipoprotein (LDL) concentrations over the 52-week treatment period. These findings suggest a potential positive impact of apremilast on both weight management and lipid profile in individuals with moderate-to-severe psoriasis in the medium-long term.

Multi-failure psoriasis patients: characterization of the patients and response to biological therapy in a multicenter Italian cohort.

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.

Long-Term Drug Survival and Effectiveness of Secukinumab in Patients with Moderate to Severe Chronic Plaque Psoriasis: 42-Month Results from the SUPREME 2.0 Study.

Purpose: SUPREME, a phase IIIb study conducted in Italy, demonstrated safety and high efficacy of secukinumab for up to 72 weeks in patients with moderate-to-severe plaque-type psoriasis. SUPREME 2.0 study aimed to provide real-world data on the long-term drug survival and effectiveness of secukinumab beyond 72 weeks. Patients and Methods: SUPREME 2.0 is a retrospective observational chart review study conducted in patients previously enrolled in SUPREME study. After the end of the SUPREME study, eligible patients continued treatment as per clinical practice, and their effectiveness and drug survival data were retrieved from medical charts. Results: Of the 415 patients enrolled in the SUPREME study, 297 were included in SUPREME 2.0; of which, 210 (70.7%) continued secukinumab treatment throughout the 42-month observation period. Patients in the biologic-naïve cohort had higher drug survival than those in the biologic-experienced cohort (74.9% vs 61.7%), while HLA-Cw6-positive and HLA-Cw6-negative patients showed similar drug survival (69.3% and 71.9%). After 42 months, Psoriasis Area and Severity Index (PASI) 90 was achieved by 79.6% of patients overall; with a similar proportion of biologic-naïve and biologic-experienced patients achieving PASI90 (79.8% and 79.1%). The mean absolute PASI score reduced from 21.94 to 1.38 in the overall population, 21.90 to 1.24 in biologic-naïve and 22.03 to 1.77 in biologic-experienced patients after 42 months. The decrease in the absolute PASI score was comparable between HLA-Cw6-positive and HLA-Cw6-negative patients. The baseline Dermatology Life Quality Index scores also decreased in the overall patients (10.5 to 2.32) and across all study sub-groups after 42 months. Safety was consistent with the known profile of secukinumab, with no new findings. Conclusion: In this real-world cohort study, secukinumab showed consistently high long-term drug survival and effectiveness with a favourable safety profile.

Clinical Features and Response to Treatment in Elderly Subjects Affected by Hidradenitis Suppurativa: A Cohort Study.

Hidradenitis suppurativa (HS) is a chronic-relapsing inflammatory skin disease. It usually appears in the second and third decades, but a smaller proportion of patients develop late-onset HS. Geriatric HS, defined as the persistence or the development of HS after the age of 65 years, has been poorly explored. This study aimed to investigate the clinical features, treatment management and response to therapies of HS elderly subjects (≥65 years old). We designed a multicentric observational study, gathering data from seven Italian university hospitals. Demographic and clinical data of HS patients aged over 65 years were collected at baseline, week 12 and week 24. Overall, 57 elderly subjects suffering from HS were enrolled. At baseline, disease severity was predominantly moderate-to-severe, with 45.6% of patients classified as Hurley III. The gluteal phenotype was the most frequently observed; it also appeared to affect patients' quality of life more than other phenotypes. Gluteal involvement was detected in about half (49.1%) of cases and associated with severe stages of the disease. In terms of therapeutic response, Hurley III patients showed the persistency of higher values of mean IHS4, DLQI, itch- and pain-NRS scores compared to Hurley I/II. In conclusion, disease severity in this subpopulation appears high and treatment is often challenging.

12th European Hidradenitis Suppurativa (EHSF) e.V. Conference-Facing HS according to the Renessaince style.

The-first hybrid-12th Conference of the European Hidradenitis Suppurativa Foundation (EHSF) e.V. took place on 8-10 February 2023 in Florence, Italy. With 198 high level scientific contributions and 757 participants from 45 countries, this 12th EHSF e.V. Conference has already been added to the EHSF's most unforgettable scientific activities. Twenty two active contributors were scientists and students under the age of 30 years and concurred for the three Young Investigator Awards. This special issue of Experimental Dermatology includes extended abstracts of the majority of the scientific lectures and posters. The 13th EHSF Conference will take place on February 7-9, 2024, as a physical presence event in Lyon, France. Dr. Philippe Guillem, Prof. Axel Villani and their team are glad to become your hosts.

Estimation of patients with psoriasis potentially eligible and currently untreated with biological drugs in Italy.

BACKGROUND: Psoriasis (PSO) patients can benefit from the growing availability of novel biological agents, that are often underused or discontinued. This real-world analysis estimated PSO patients potentially eligible and currently untreated with biologics in Italy. METHODS: An observational analysis was performed on administrative databases of a pool of healthcare entities, covering 11.3% of Italian population. During the inclusion period (2010- 2020), patients were identified by: 1) at least one prescription of topical drugs for PSO; or 2) active exemption for PSO; or 3) at least one PSO hospital discharge diagnosis. The index-date was the first PSO identification across inclusion period. Eligibility for biologics was evaluated prior to index-date (characterization period) through two not-mutually exclusive criteria: Criterion A, failure of at least one systemic treatment, and/or Criterion B, onset of psoriatic arthritis (PsA). Data were re-proportioned to the Italian population. RESULTS: The study sample showed a PSO prevalence of 2%. Projection to 2020 national population (N=59,236.213) estimated 1.43 million Italian patients affected by PSO: 95% treated with conventional therapies, 4% with biologics, and 1% untreated. Among those non-treated with biologics, 3.8% of overall PSO patients met one or both eligibility criteria for biologics, specifically 25% met criterion A (failure to conventional treatments), 68% criterion B (PsA co-diagnosis), and 7% met both. About half of them had 1 or 2 comorbidities and 30% above 3. CONCLUSIONS: These findings from real clinical practice estimated about 4% PSO patients potentially eligible for biologics, but still untreated, with nearly one-third exhibiting a complex comorbidity profile.

Anti-Interleukin-17s for successful management of pustular psoriasis.

Generalised pustular psoriasis (GPP) and acrodermatitis continua of Hallopeau (ACH) are two rare entities included in the spectrum of pustular psoriasis (PP). Due to the lack of randomised controlled clinical trials and standardized guidelines, their treatment remains a challenge for clinicians. Thus, herein we report our centre experience with the successful use of interleukin (IL)-17 inhibitors in three patients affected by PP. We also provide a brief overview of the current knowledge concerning the role of IL-17 in PP pathogenesis and of the use of IL-17 inhibitors in the treatment of PP. Based on our experience, anti-IL-17 molecules may represent a valuable therapeutical option for patients affected by different PP subtypes.

The Relevant Oral Burden of Patients with Hidradenitis Suppurativa.

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.

Clinical and Ultrasonographic Characterization of Hidradenitis Suppurativa in Female Patients: Impact of Early Recognition of the Disease.

Hidradenitis suppurativa (HS) is considered a post-pubertal disease; however, earlier onset is not infrequent. The burden of HS on the female population is very relevant, and early identification might reduce the quality of life impairment and improve the therapeutic approach. In this study, we investigated clinical biomarkers of HS that could impact the management of patients affected by HS. Female patients affected by stable HS were prospectively included in this study. Anamnestic data, clinical and ultrasonographic features were collected and analyzed. Overall, 53 patients were included in this study. The median age of onset was 19 (IQR: 14-25). Early onset was reported by 22/53 patients (median age of onset: 14; IQR: 11-16). Four patients had pre-menstruation occurrence. Early-onset patients had an earlier first-menstrual-cycle age and more frequent genital localization of HS, and were more often treated with biologics. Patients with early-onset-HS and genital localization had more severe disease with a higher number of areas affected, Hurley, and IHS4 scores. Genital involvement might be prevalent in patients with early-onset HS, leading to a worse impact on the global severity of the disease and tailored treatment protocols, including multidisciplinary approaches, in order to improve the early recognition of hidden lesions.

Real-world use of dimethyl fumarate in patients with plaque psoriasis: a Delphi-based expert consensus.

Dimethyl fumarate (DMF) was recently approved by the European Medicines Agency for systemic treatment of moderateto- severe chronic plaque psoriasis. Appropriate management of DMF treatment is required to achieve optimal clinical benefits. 7 dermatology experts gathered online for 3 meetings to identify consensus on the use of DMF in patient selection, drug dosage/titration, side effects management, and follow-up, with the aim to provide guidance on the use of DMF for psoriasis in clinical dermatological practice based on literature data and expert opinion. 20 statements were discussed and voted on using a facilitator- mediated modified Delphi methodology. Strong consensus was reached for all statements (agreement level of 100%). DMF treatment is characterized by dosage flexibility, sustained efficacy, high rates of drug survival, and low potential for drug-drug interactions. It can be used in a broad range of patients, including the elderly or those with comorbidities. Side effects (mainly gastrointestinal disorders, flushing, and lymphopenia) are frequently reported but are generally mild and transient and can be minimized by dosage adjustments and a slow titration schedule. Hematologic monitoring throughout the treatment course is required to reduce the risk of lymphopenia. This consensus document provides clinical dermatologists with answers on the optimal use of DMF to treat psoriasis.

Pso-Reg: a web registry for psoriasis in real life.

BACKGROUND: Psoriasis (PsO) is a common immune mediated inflammatory disease, affecting about 60 million people worldwide. Although current therapies have dramatically changed the therapeutic approach to the disease, the heterogeneity of responses often results in an essential unmet clinical need. This study describes the design and development of the Psoriasis Registry (Pso-Reg), an Italian electronic-based-registry, aimed to collect real life data of patients with psoriasis. METHODS: Pso-Reg is a multicenter, retrospective and observational cohort study based on the Research Electronic Data Capture (REDcap) tool. Five Italian medical centres were part of the network and all patients affected by PsO were included in the study. Socio-demographic, clinical characteristics, laboratory findings and therapies were collected, and descriptive analysis was carried out. RESULTS: Among the 768 patients analyzed, 446 were men (58.1%), with a mean age of 55.5 years. The first more frequent comorbidity was psoriatic arthritis (26.8%), followed by hypertension (25.3%), diabetes (10%) and dyslipidemia (11.7%). Of the entire cohort, 240 patients (38.2%) had a positive family history for PsO. Vulgar type was the most common phenotype (85.5%), with a major involvement of the scalp (13.8%). The mean PASI (Psoriasis Area Severity Index) score at the baseline was 7.5 (7.8). At the enrolment, 107 patients were treated with topic treatments (13.9%), 5 with phototherapy (0.7%), 92 with cDMARDs (conventional disease-modifying anti-rheumatic drugs) (12.0%) and 471 with biologic therapies (61.3%). CONCLUSIONS: Real-life data from Pso-Reg could contribute providing the rationale for an individual-based strategy and a more tailored approach for the management of psoriasis.

Brodalumab for the Treatment of Moderate-to-Severe Psoriasis: An Expert Delphi Consensus Statement.

Brodalumab is a recombinant, fully human immunoglobulin IgG2 monoclonal antibody specifically targeted against interleukin-17RA that has been approved for the treatment of moderate-to-severe psoriasis in Europe. We developed a Delphi consensus document focused on brodalumab for the treatment of moderate-to-severe psoriasis. Based on published literature and their clinical experience a steering committee drafted 17 statements covering 7 domains specific to the treatment of moderate-to-severe psoriasis with brodalumab. A panel of 32 Italian dermatologists indicated their level of agreement using a 5-point Likert scale (from 1 = "strongly disagree" to 5 = "strongly agree") using an online modified Delphi method. After the first round of voting (32 participants), positive consensus was reached for 15/17 (88.2%) of the proposed statements. Following a face-to-face virtual meeting, the steering committee decided that 5 statements would form "main principles" and 10 statements formed the final list. After a second round of voting, consensus was reached in 4/5 (80%) of the main principles and 8/10 (80%) for consensus statements. The final list of 5 main principles and 10 consensus statements identify key indications specific to the use of brodalumab in the treatment of moderate-to-severe psoriasis in Italy. These statements aid dermatologists in the management of patients with moderate-to-severe psoriasis.