RIPK4 regulates cell-cell adhesion in epidermal development and homeostasis.

Epidermal development and maintenance are finely regulated events requiring a strict balance between proliferation and differentiation. Alterations in these processes give rise to human disorders such as cancer or syndromes with skin and annexes defects, known as ectodermal dysplasias (EDs). Here, we studied the functional effects of two novel receptor-interacting protein kinase 4 (RIPK4) missense mutations identified in siblings with an autosomal recessive ED with cutaneous syndactyly, palmoplantar hyperkeratosis and orofacial synechiae. Clinical overlap with distinct EDs caused by mutations in transcription factors (i.e. p63 and interferon regulatory factor 6, IRF6) or nectin adhesion molecules was noticed. Impaired activity of the RIPK4 kinase resulted both in altered epithelial differentiation and defective cell adhesion. We showed that mutant RIPK4 resulted in loss of PVRL4/nectin-4 expression in patient epidermis and primary keratinocytes, and demonstrated that PVRL4 is transcriptionally regulated by IRF6, a RIPK4 phosphorylation target. In addition, defective RIPK4 altered desmosome morphology through modulation of plakophilin-1 and desmoplakin. In conclusion, this work implicates RIPK4 kinase function in the p63-IRF6 regulatory loop that controls the proliferation/differentiation switch and cell adhesion, with implications in ectodermal development and cancer.

Autoreactivity to self-antigens LL37 and ADAMTSL5 influences the clinical response to risankizumab in psoriatic patients.

The autoantigens LL37 and ADAMTSL5 contribute to induce pathogenetic T-cells responses in a subset of psoriatic patients. Whether the presence of LL37-and/or ADAMTS5-reactive T-cells influences the clinical response to treatment is still unknown. The aim of the study is to evaluate the clinical responses to the anti-IL-23 risankizumab in LL37 and/or ADAMTSL5-reactive patients in comparison with non-reactive ones and to assess whether genetics (HLA-Cw06.02) or BMI influences the response to treatment. Patients were screened at baseline for the presence of circulating LL37 or/and ADAMTSL5-reactive T-cells and were treated as per protocol with risankizumab. Effectiveness data (PASI scores) were collected at weeks 4, 16, 28, 40 and 52. Data were also analyzed based on HLA-Cw06.02 status and BMI. The overall response to treatment of patients with autoreactivity to LL37 or ADAMTSL5 did not differ compared to the non-reactive cohort as measured as PASI75/90/100 at different time points; however, subjects that had autoreactive T-cells to both LL37 and ADAMTS5 demonstrated suboptimal response to treatment starting at week16. HLA-Cw06:02+ patients demonstrated faster response to risankizumab at week 4 compared to HLA-Cw06:02-. Additionally, the response to treatment was influenced by the BMI with slower responses seen in overweight and obese patients at week 4 and week16. In conclusion, while the presence of either LL37-and ADAMTS5-reactive circulating T-cells do not influence the clinical response to risankizumab, the presence of the double reactivity to both LL37 and ADAMTS5 decreases the clinical responses. Moreover, we evidenced that HLA-Cw06+ respond faster to IL-23 inhibition and that BMI, associated to autoreactivity, can influence the speed in response.

Risk of peripheral neuropathy in patients with psoriasis and psoriatic arthritis. A prospective cohort study.

INTRODUCTION/AIMS: Laboratory and clinical data suggest a link between neurologically mediated inflammation and psoriasis, but the risk and features of peripheral neuropathy in psoriasis or psoriatic arthritis remain unknown. The aim of this exploratory study was to evaluate the risk and to describe the features of peripheral neuropathy in patients with psoriasis and psoriatic arthritis. METHODS: One hundred patients with psoriasis and/or psoriatic arthritis and 100 control subjects were consecutively enrolled. Diagnostic confirmation included electrophysiological examination, skin biopsy, and nerve ultrasound for confirmed polyneuropathy. RESULTS: Nine patients were diagnosed with confirmed polyneuropathy, while none of the control subjects had the condition (relative risk [RR] = 19.00, 95% confidence interval [CI] = 1.12-322.11). Specific relative risks for polyneuropathy were 22.09 (95% CI = 1.17-416.43) in psoriasis patients and 18.75 (95% CI = 1.07-327.62) in psoriatic arthritis patients. The observed polyneuropathy in all nine patients was length-dependent, symmetrical, and predominantly sensory, with minimal or no disability. Comorbidities and exposure to therapies known to increase the risk of polyneuropathy were more frequent in psoriasis and/or psoriatic arthritis patients compared to controls (42% vs. 4%, p = .0001). Analyzing data after excluding possible contributory causes, the risk of polyneuropathy in patients with psoriasis and/or psoriatic arthritis was not significant. DISCUSSION: Psoriasis and psoriatic arthritis appear to be associated with an increased risk of polyneuropathy. This increased risk seems to be linked to the higher prevalence of contributing factors for polyneuropathy, rather than a direct increase in neuropathy risk specifically related to psoriasis and psoriatic arthritis.

Association between maternal dupilumab exposure and pregnancy outcomes in patients with moderate-to-severe atopic dermatitis: A nationwide retrospective cohort study.

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.

Dupilumab significantly improves sleep in adults with atopic dermatitis: results from the 12-week placebo-controlled period of the 24-week phase IV randomized double-blinded placebo-controlled DUPISTAD study.

BACKGROUND: Sleep disturbance is a prominent symptom of atopic dermatitis (AD) and can result in insomnia, daytime fatigue, drowsiness, reduced productivity and impaired quality of life (QoL). OBJECTIVES: The Dupilumab Effect on Sleep in AD Patients (DUPISTAD) phase IV randomized double-blinded placebo-controlled study evaluated the impact of dupilumab treatment on sleep and other patient- and physician-reported outcomes. METHODS: Adults with moderate-to-severe AD were randomized 2 : 1 to dupilumab 300 mg once every 2 weeks (q2w) or placebo for 12 weeks; concomitant topical corticosteroids were permitted. Patients subsequently entered an open-label phase and received dupilumab 300 mg q2w for a further 12 weeks. The primary endpoint was the percentage change in sleep quality from baseline to week 12, assessed using a novel numeric rating scale (NRS). Secondary and exploratory endpoints included percentage change in peak pruritus NRS (PP NRS), change in SCORing Atopic Dermatitis (SCORAD), SCORAD sleep visual analogue scale (VAS), Eczema Area and Severity Index, Patient-Reported Outcomes Measurement Information System (PROMIS) sleep-related impairment T-score and the Epworth Sleepiness Scale. Sleep diary and wrist actigraphy measurements were recorded throughout the study. RESULTS: In total, 127 patients received dupilumab and 61 patients received placebo. Demographic and baseline disease characteristics were balanced between groups. Sleep quality NRS significantly improved in patients treated with dupilumab by week 12 vs. placebo [least squares mean of the difference (LSMD) -15.5%, P < 0.001]. PP NRS (LSMD -27.9%, P < 0.001), SCORAD (LSMD -15.1, P < 0.001), SCORAD sleep VAS (LSMD -2.1, P < 0.001) and PROMIS T-score (LSMD -3.6, P < 0.001) were also significantly improved at week 12 with dupilumab vs. placebo. The overall percentage of patients reporting treatment-emergent adverse events was lower in the dupilumab group (56.7%) than in the placebo group (67.2%). CONCLUSIONS: Dupilumab significantly improved sleep quality and perception of sleep continuity, itch, metrics of AD severity and QoL in adults with moderate-to-severe AD, with an acceptable safety profile compared with placebo.

Tildrakizumab improves high burden skin symptoms, impaired sleep and quality of life of moderate-to-severe plaque psoriasis patients in conditions close to clinical practice.

BACKGROUND: Tildrakizumab (TIL) is an interleukin (IL)-23p19 inhibitor for the treatment of moderate-to-severe plaque psoriasis with long-term efficacy and safety demonstrated in Phase III trials. Studies conducted in conditions closer to clinical practice are needed. OBJECTIVES: The TRIBUTE study (open-label, Phase IV) assessed the efficacy and impact on health-related quality of life (HRQoL) of TIL 100 mg in adult moderate-to-severe psoriasis patients (naïve to IL-23/Th17 pathway inhibitors) in conditions similar to clinical practice. METHODS: Key efficacy measure was Psoriasis Area Severity Index (PASI). HRQoL was evaluated using the Dermatology Life Quality Index (DLQI) and Skindex-16. Additional patient-reported outcomes included Pain-, Pruritus- and Scaling-Numerical Rating Scale (NRS), Medical Outcome Study (MOS)-Sleep, Work Productivity and Activity Impairment (WPAI), Patient Benefit Index (PBI) and Treatment Satisfaction Questionnaire for Medication (TSQM). RESULTS: One hundred and seventy-seven patients were enrolled (six patients did not complete the study). After 24 weeks, the proportion of patients achieving PASI scores ≤ 3, PASI 75, PASI 90 and DLQI 0/1 was 88.4%, 92.5%, 74.0% and 70.4%, respectively. Skindex-16 overall score improved (mean absolute change from baseline, MACB [95%CI]: -53.3 [-58.1, -48.5]). Significant benefits (MACB [95%CI]) were found on pruritus-, pain- and scaling-NRS scores (-5.7 [-6.1, -5.2], -3.5 [-4.1, -3.0] and -5.7 [-6.2, -5.2], respectively), MOS-Sleep (-10.4 [-13.3, -7.4] Sleep problems Index II) and WPAI (-36.4 [-42.6, -30.2] activity impairment, -28.2 [-34.7, -21.7] productivity loss, -27.0 [-32.9, -21.1] presenteeism and -6.8 [-12.1, -1.5] absenteeism). 82.7% of patients reported PBI ≥ 3 and the mean (SD) global TSQM score was high (80.5 [18.5]). Only one serious treatment-emergent adverse event was reported (not-related to TIL). CONCLUSIONS: TIL 100 mg treatment after 24 weeks in conditions close to real clinical practice showed a quick and high improvement in psoriasis signs and HRQoL. Patient reported improvements in sleep outcomes and work productivity, relevant benefits and high treatment satisfaction. The safety profile was favourable and consistent with Phase III trials.

Secukinumab demonstrates superiority over narrow-band ultraviolet B phototherapy in new-onset moderate to severe plaque psoriasis patients: Week 52 results from the STEPIn study.

BACKGROUND: Biologic treatments have been studied mainly in patients with a long-term history of psoriasis and previous treatment failures. OBJECTIVES: The purpose of this primary analysis of the STEPIn study is to determine whether early intervention with secukinumab in patients with new-onset moderate to severe plaque psoriasis is superior to standard of care treatment with narrow band ultraviolet B (nb-UVB) phototherapy. METHODS: The STEPIn study is a randomized, open-label, multicentre study to investigate early intervention with 52 weeks of secukinumab 300 mg administered subcutaneously versus standard treatment with nb-UVB phototherapy in patients with new-onset (≤12 months) moderate to severe plaque psoriasis (NCT03020199). The primary and additional secondary endpoints were ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) at Week 52 and Investigator's Global Assessment (IGA mod 2011) 0/1 response at Week 52, respectively. RESULTS: In the secukinumab and nb-UVB study arms, 77/80 and 76/80 randomized patients received at least one dose of study treatment, respectively. The primary endpoint was achieved: 91.1% (70/77) of patients achieved a PASI 90 response at Week 52 in the secukinumab arm versus 42.3% (32/76) in the nb-UVB arm (p < 0.0001, odds ratio [OR] estimate [95% confidence intervals, CI] = 16.3 [5.6, 46.9]). The additional secondary endpoint was also achieved: 85.7% of patients achieved an IGA 0/1 response at Week 52 in the secukinumab arm versus 36.8% in the nb-UVB arm (p < 0.0001). The safety data were consistent with the safety profiles of secukinumab and nb-UVB with no new or unexpected safety signals. CONCLUSIONS: Secukinumab was superior to nb-UVB in treating patients with new-onset moderate to severe plaque psoriasis. The high and sustained skin clearance observed indicates that biologic treatment for psoriasis may be more effective if used early in the disease course.

Real-life effectiveness of tildrakizumab in chronic plaque psoriasis: A 52-week multicentre retrospective study-IL PSO (Italian landscape psoriasis).

BACKGROUND: Tildrakizumab is a humanized monoclonal antibody that binds selectively the p19 subunit of interleukin-23. It is approved for treatment of moderate-severe chronic plaque psoriasis. OBJECTIVES: We conducted a 52-week retrospective study to assess the effectiveness and safety of tildrakizumab in a real-life setting. METHODS: Our retrospective study included 237 consecutive adults with moderate-to-severe plaque psoriasis, enrolled in 10 different Italian centres, treated with tildrakizumab up to Week 52. Patient characteristics, comorbidities, previous treatments and the PASI (Psoriasis Area and Severity Index) score at each visit (baseline, Week 16, Week 28 and Week 52) were retrieved from the electronic medical records. The percentages of patients achieving 75%, 90% and 100% (PASI 75, PASI 90 and PASI 100) improvement in PASI with respect to baseline PASI were registered. RESULTS: At Week 52, 90.91%, 73.55% and 58.68% of patients achieved a PASI reduction ≥75% (PASI 75), PASI 90 and PASI 100, respectively. An absolute PASI ≤ 2 was reached by 85.95% at Week 52. Compared with Phase 3 clinical trials, we observed similar rates of PASI 75/90 responses and higher percentages of patients achieving PASI 100. Patients who had not responded to previous biologic treatments and patients with cardio-metabolic comorbidities were significantly more likely to achieve PASI 100 at Week 28 and PASI 90 at Week 52. The higher body mass index did not interfere with the odds of reaching PASI 75/90/100 at each time point. No significant safety findings were recorded throughout the study, and none of the patients had to interrupt the treatment because of adverse events. CONCLUSION: Our data suggest that the efficacy of tildrakizumab for plaque psoriasis in 'real-life' clinical practice is comparable with Phase 3 clinical trials with higher percentages of patients achieving complete skin clearance (PASI 100) at Weeks 16, 28 and 52.

Real-life effectiveness and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: A 104-week multicenter retrospective study - IL PSO (ITALIAN LANDSCAPE PSORIASIS).

BACKGROUND: Guselkumab is a fully human monoclonal antibody that binds selectively to the p19 subunit of interleukin-23, which has shown efficacy in patients with previous incomplete response to ustekinumab in the NAVIGATE clinical trial. [Correction added on [28-02-2023], after first online publication: 'humanized monoclonal antibody' has been changed to 'fully human monoclonal antibody' in the preceding sentence.] OBJECTIVES: We conducted a 104-week multicenter retrospective study to assess the effectiveness and safety of guselkumab in patients affected by plaque psoriasis with an inadequate response to ustekinumab in a real-life setting. METHODS: Our retrospective study included 233 adults affected by moderate-to-severe plaque psoriasis, enrolled in 14 different Italian centres, and treated with guselkumab after failing therapy with ustekinumab. Patient characteristics and PASI (Psoriasis Area and Severity Index) score at each visit (baseline, weeks 16, 52 and 104) were recorded. The percentages of patients achieving 75%, 90% and 100% (PASI 75, PASI 90 and PASI 100) improvement in PASI, compared with baseline, were registered. RESULTS: At week 52, PASI 75 was reached by 89.88% of patients, PASI 90 by 71.43%, PASI 100 by 58.83% and absolute PASI ≤2 by 90.48%. At week 104, similar effectiveness results were observed. Compared to the NAVIGATE trial, we observed higher rates of PASI 75/90/100. Patients with the involvement of difficult-to-treat areas were significantly less likely to achieve PASI90 and PASI100 at week 16. Obese patients had significantly lower rates of PASI75 and PASI ≤2 at week 52. At week 104, comparable responses were observed among all patients' subgroups, regardless of BMI status, involvement of difficult-to-treat areas, presence of cardiometabolic comorbidities and concomitant psoriatic arthritis. No significant safety findings were reported throughout the study. CONCLUSION: Our data suggest that the efficacy of guselkumab in patients with inadequate response to ustekinumab for plaque psoriasis in 'real-life' clinical practice is comparable with NAVIGATE study with higher percentages of patients achieving PASI90 and PASI100 at weeks 16, 52 and 104.

Upadacitinib plus topical corticosteroids in atopic dermatitis: Week 52 AD Up study results.

BACKGROUND: Primary (week 16) results from the ongoing phase 3, double-blind AD Up study (NCT03568318) demonstrate a positive benefit-risk profile for upadacitinib + topical corticosteroid (TCS) in patients with moderate-to-severe atopic dermatitis. OBJECTIVE: We evaluated the efficacy and safety of upadacitinib + TCS through 52 weeks. METHODS: Patients aged 12 to 75 years with chronic moderate-to-severe atopic dermatitis (≥10% of body surface area affected, Eczema Area and Severity Index [EASI] ≥16, Validated Investigator's Global Assessment for atopic dermatitis [vIGA-AD] ≥3, and Worst Pruritus Numerical Rating Scale [WP-NRS] score ≥4) were randomized 1:1:1 to once-daily upadacitinib 15 mg + TCS, upadacitinib 30 mg + TCS, or placebo (PBO) + TCS (rerandomized at week 16 to upadacitinib + TCS). Safety and efficacy, including proportion of patients experiencing ≥75% improvement in EASI (EASI-75), vIGA-AD of clear/almost clear with improvement ≥2 grades (vIGA-AD 0/1), and WP-NRS improvement ≥4, were assessed through week 52. Missing data were primarily handled by nonresponse imputation incorporating multiple imputation for missing values due to coronavirus disease 2019 (COVID-19). RESULTS: Of 901 patients, 300 were randomized to upadacitinib 15 mg + TCS, 297 to upadacitinib 30 mg + TCS, and 304 to PBO + TCS. For all end points, efficacy for upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS at week 16 was maintained through week 52. At week 52, the proportions of patients treated with upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS who experienced EASI-75 were 50.8% and 69.0%, respectively; 33.5% and 45.2%, respectively, experienced vIGA-AD 0/1; and 45.3% and 57.5%, respectively, experienced WP-NRS improvement ≥4. Upadacitinib + TCS was well tolerated through 52 weeks; no new important safety risks beyond the current label were observed. No deaths were reported; major adverse cardiovascular events and venous thromboembolic events were infrequent (≤0.2/100 patient-years). CONCLUSIONS: Results through 52 weeks demonstrate long-term maintenance of efficacy and a favorable safety profile of upadacitinib + TCS in patients with moderate-to-severe AD.

Real-life efficacy of guselkumab in patients with early psoriatic arthritis.

OBJECTIVES: To assess the efficacy of the novel anti-IL-23 monoclonal antibody guselkumab in a real-life observational cohort of patients with early PsA. METHODS: We conducted an observational study on patients with early PsA followed by the joint dermatology-rheumatology clinics of two Italian centres starting therapy with guselkumab for severe skin involvement. Each patient was evaluated at baseline and every 24 weeks for one year, recording Disease Activity Index for PsA (DAPSA), PASI, VAS Pain, VAS Prutitus, Patient's Global Assessment (PtGA) and assessing DAPSA response. RESULTS: Twenty-four patients were recruited (16 women). The mean duration of skin disease was 12.5 years (CI 8; 17), but all patients had a shorter articular disease duration, 21.29 months (CI 15.9; 26.68). At baseline, all patients displayed a moderate cutaneous disease with a mean PASI of 15.2 (CI 11.7-18.6) and high disease activity, characterized by mean DAPSA of 26.84 (CI 22.49-31.19). An inflammatory low back pain was reported by five patients (20%) with a mean BASDAI 5.1 (CI 4,38-5,85) at baseline. The majority of guselkumab-treated patients (n = 18; 75%) reached DAPSA remission or DAPSA low disease activity after six months. Seventeen out of 24 patients completed 12 months of treatment, 11 of them (65%) in low disease activity, six (35%) in remission. All patients with axial disease reported improvement of inflammatory low back pain at week 24 with a mean BASDAI 2.98 (CI 2,18- 3,77). No significant side effects were reported. CONCLUSIONS: Real-life data on a cohort of early PsA patients confirm the efficacy and safety of guselkumab on peripheral and axial manifestations.

The biological basis of disease recurrence in psoriasis: a historical perspective and current models.

A key challenge in psoriasis therapy is the tendency for lesions to recur in previously affected anatomical locations after treatment discontinuation following lesion resolution. Available evidence supports the concept of a localized immunological 'memory' that persists in resolved skin after complete disappearance of visible inflammation, as well as the role of a specific subpopulation of T cells characterized by the dermotropic CCR4+ phenotype and forming a local memory. Increasing knowledge of the interleukin (IL)-23/T helper 17 (Th17) cell pathway in psoriasis immunopathology is pointing away from the historical classification of psoriasis as primarily a Th1-type disease. Research undertaken from the 1990s to the mid-2000s provided evidence for the existence of a large population of CD8+ and CD4+ tissue-resident memory T cells in resolved skin, which can initiate and perpetuate immune responses of psoriasis in the absence of T-cell recruitment from the blood. Dendritic cells (DCs) are antigen-presenting cells that contribute to psoriasis pathology via the secretion of IL-23, the upstream regulator of Th17 cells, while plasmacytoid DCs are involved via IL-36 signalling and type I interferon activation. Overall, the evidence discussed in this review indicates that IL-23-driven/IL-17-producing T cells play a critical role in psoriasis pathology and recurrence, making these cytokines logical therapeutic targets. The review also explains the clinical efficacy of IL-17 and IL-23 receptor blockers in the treatment of psoriasis.

Anti-IL17 and anti-IL23 biologic drugs for scalp psoriasis: A single-center retrospective comparative study.

Scalp is a frequent localization of psoriasis that has a massive impact on patient's quality of life. Managing this psoriasis' manifestation is often challenging, thus biologic drugs are widely used as a treatment option in refractory scalp psoriasis. The aim of our study is to retrospectively compare the efficacy of anti-interleukin (IL) 23 drugs (guselkumab, tildrakizumab, risankizumab) and anti-IL17 or anti-IL17RA biologics (secukinumab, ixekizumab, and brodalumab) in real-life patients affected by scalp psoriasis. One hundred twenty-seven patients with a clinical diagnosis of scalp psoriasis and a baseline scalp Physician Global Assessment ≥3 were enrolled; 65 patients were treated with anti-IL23 and anti-IL62 with anti-IL17 or anti-IL17RA. Statistical analysis trough χ2 test was performed in order to evaluate the percentage of response among the two groups of patients. Responders' percentage of patients under anti-IL23 was 41.5%, 75.4%, 88.1%, 87.5%, 93.7%, and 100% at Week 4, 16, 48, 96, and 144, respectively. In the group on anti-IL17 was 62.9%, 90.3%, 91.2%, 97.3%, 96.9%, and 95.2% at Week 4, 16, 48, 96, and 144, respectively. Both anti-IL17 and anti-IL23 appeared to be effective on scalp psoriasis; in particular patients treated with anti-IL17 drugs reached a faster significant reduction of the lesions; on the other hand, anti-IL23 monoclonal antibodies were slightly superior in maintaining the clinical improvement through the follow-up.

Apremilast for the treatment of palmo-plantar non-pustular psoriasis: A real-life single-center retrospective study.

Palmoplantar psoriasis (PP) is a type of psoriasis that involves the skin of the palms and soles and can present as hyperkeratotic, similar to the vulgaris psoriasis of the body. Apremilast, as an oral inhibitor of phosphodiesterase 4 (PDE4), is currently approved for the treatment of psoriatic arthritis and for moderate-to-severe psoriasis in adult patients who have not responded or have contraindications or do not tolerate other systemic treatments. We evaluated the efficacy and safety of apremilast in the treatment of non-pustular palmo-plantar psoriasis in a cohort of 12 patients. We found a clinical response of clear/almost clear palmoplantar psoriasis (PPPGA score 0/1) in 83.33% of our patients, at week 16. No significant safety issues were reported and none of our patients had to discontinue the drug.

Real life long-term efficacy and safety of ixekizumab in moderate-to-severe psoriasis: A 192 weeks multicentric retrospective study-IL PSO (Italian landscape psoriasis).

Psoriasis is one of the commonest inflammatory skin diseases determining a very high impact on patients' quality of life and daily activities and relationships. Several biologic therapies have been approved through the years for the treatment of moderate-to-severe plaque psoriasis, and efficacy and safety profile have been analyzed in clinical trials. Ixekizumab is an immunoglobulin G subclass 4 monoclonal antibody that selectively targets and binds IL-17A with high specificity and affinity. Inhibiting IL-17A activity, ixekizumab reduces and turns down levels of inflammation, resulting in the clinical improvement of the disease. Long-term efficacy and safety profile of ixekizumab have been investigated and reported in the UNCOVER trials, but in literature there are only few studies based on real life experience. We present the efficacy and safety profile of ixekizumab in a cohort of 779 patients affected by moderate-to-severe plaque psoriasis and treated with ixekizumab in 11 Italian dermatology hospitals, with a follow-up of care until 192 weeks.

Real-world evidence of biologic treatments in moderate-severe psoriasis in Italy: Results of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: An obserVAtional longitudinal study of real-life clinical practice) study.

EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: An obserVAtional (CANOVA) study was aimed at providing real-world evidence of the effectiveness of biologics in Italian patients with moderate-severe psoriasis. It was an observational, retro-prospective cohort study conducted in 17 Italian dermatology clinics. Adult patients with moderate-severe plaque psoriasis, who started a biologic treatment between 24 weeks and 24 months before enrolment, were included. With a follow-up visit at 6 months after enrolment, each patient had at least 12 months of observation. The primary objective was to describe the clinical response rates (PASI 75) after 16/24/52 weeks from biologic treatment start. Secondary outcomes were sustained response, quality of life, and treatment satisfaction. Of the 669 eligible patients (64% males), 52% were naïve to biologics, though a mean duration of psoriasis since first diagnosis of 18.6 years (SD 13.2). The most frequently prescribed biologics were secukinumab (41%), ustekinumab (25%), TNF-inhibitors (22%) and ixekizumab (12%). PASI 75 was achieved by 86% of patients (95% CI: 82%-89%) at 16 weeks, 90% (87%-93%) at 24 weeks, and 91% (89%-94%) at 52 weeks. Patients achieving PASI 90 and PASI 100 at 52 weeks were 75% (71%-79%) and 53% (49%-57%), respectively. Sustained PASI 75 response after 1 year from treatment start was achieved by 78% (74%-82%) of patients. Mean DLQI total score was 2.3 (SD 3.9) at enrollment and decreased at the final visit to 1.8 (3.6). A high level of treatment satisfaction was expressed by patients over the study period. This large real-world study confirms in the clinical practice the good effectiveness and acceptability of biologics in psoriasis patients.

Real-World Treatment Patterns and Treatment Benefits among Adult Patients with Atopic Dermatitis: Results from the Atopic Dermatitis Patient Satisfaction and Unmet Need Survey.

Atopic dermatitis is a chronic inflammatory skin disorder associated with a heterogeneous presentation and considerable disease burden. Exploring atopic dermatitis treatment patterns and patient benefits could improve disease management and patients' quality of life. This study aimed to describe current and previous atopic dermatitis treatment patterns and patient benefits from those treatments to inform disease management. Data were collected in 10 countries. Adults (n = 1,988) with confirmed moderate-to-severe atopic dermatitis completed a web-based cross-sectional survey. Most patients (86.6%) had body surface area involvement <10%, and therapies used were topical (69.7%), systemic (28.1%), and biologics (2.3%). Most flares were managed by topical monotherapies (73.4%), even in patients with body surface area involvement ≥10%. Treatment expectations were met only partially, or not at all, in 75% of patients. Those with body surface area involvement ≥10% reported lower treatment satisfaction. Overall, this study highlights the unmet medical needs in atopic dermatitis management.

Comparative effectiveness of biologics in clinical practice: week 12 primary outcomes from an international observational psoriasis study of health outcomes (PSoHO).

BACKGROUND: Clinical trials study treatment outcomes under stringent conditions, capturing incompletely the heterogeneity of patient populations and treatment complexities encountered in real-world practice. OBJECTIVES: To compare the effectiveness of anti-interleukin (IL)-17A biologics relative to other approved biologics in patients with moderate-to-severe psoriasis. METHODS: The Psoriasis Study of Health Outcomes (PSoHO) is an ongoing 3-year observational cohort study in adults with chronic moderate-to-severe plaque psoriasis initiating or switching to a new biologic. Primary study endpoint is the proportion of patients achieving 90% improvement in Psoriasis Area and Severity Index (PASI 90) and/or static Physician Global Assessment (sPGA) 0/1 at Week 12 (W12) in the anti-IL-17A cohort (ixekizumab [IXE], secukinumab) vs. all other approved biologics. Secondary outcomes include the proportion of patients who achieve PASI 75/90/100, absolute PASI scores ≤5, ≤2 and ≤1, Dermatology Life Quality Index (DLQI) score of 0/1 at W12 between the two cohorts and among the individual biologics. Comparative effectiveness analyses were conducted using Frequentist Model Averaging (FMA), a novel causal inference machine learning approach. Missing data for binary outcomes were imputed as non-response. RESULTS: Patient profiles in the anti-IL-17A cohort and other biologics cohort were similar, with more frequent comorbid psoriatic arthritis and less frequent exposure to conventional treatments in the patients receiving anti-IL-17A biologics. At W12, 71.4% of patients who received an anti-IL-17A biologic achieved PASI 90 and/or sPGA 0/1 compared to 58.6% of patients who received other biologics (odds ratios [OR], 1.9; 95% confidence intervals [CI], [1.6, 2.4]). Similar findings were observed for secondary outcomes. CONCLUSIONS: These results reflect the high efficacy and early onset of skin clearance of IL-17A inhibitors observed in randomized clinical trials and confirm the effectiveness of anti-IL-17A biologics in the real-world setting.

Urban Seismic Network Based on MEMS Sensors: The Experience of the Seismic Observatory in Camerino (Marche, Italy).

Urban seismic networks are considered very useful tools for the management of seismic emergencies. In this work, a study of the first urban seismic network in central Italy is presented. The urban seismic network, built using MEMS sensors, was implemented in the urban district of Camerino, one of the cities in central Italy with the greatest seismic vulnerability. The technological choices adopted in developing this system as well as the implemented algorithms are shown in the context of their application to the first seismic event recorded by this innovative monitoring infrastructure. This monitoring network is innovative because it implements a distributed computing and statistical earthquake detection algorithm. As such, it is not based on the traces received by the stations from the central server; rather, each station carries out the necessary checks on the signal in real time, sending brief reports to the server in case of anomalies. This approach attempts to shorten the time between event detection and alert, effectively removing the dead times in the systems currently used in the Italian national network. The only limit for an instant alarm is the latency in the tcp/ip packages used to send the short reports to the server. The presented work shows the infrastructure created; however, there is not enough data to draw conclusions on this new early warning approach in the field, as it is currently in the data collection phase.

Incidence rates of hospitalization and death from COVID-19 in patients with psoriasis receiving biological treatment: A Northern Italy experience.

INTRODUCTION: Whether biologic therapies enhance the risk of coronavirus 2019 (COVID-19) or affect the disease outcome in patients with chronic plaque psoriasis remains to be ascertained. OBJECTIVE: We sought to investigate the incidence of hospitalization and death for COVID-19 in a large sample of patients with plaque psoriasis receiving biologic therapies compared with the general population. METHODS: This is a retrospective multicenter cohort study including patients with chronic plaque psoriasis (n = 6501) being treated with biologic therapy and regularly followed up at the divisions of dermatology of several main hospitals in the Northern Italian cities of Verona, Padua, Vicenza, Modena, Bologna, Piacenza, Turin, and Milan. Incidence rates of hospitalization and death per 10,000 person-months with exact mid-p 95% CIs and standardized incidence ratios were estimated in the patients with psoriasis and compared with those in the general population in the same geographic areas. RESULTS: The incidence rate of hospitalization for COVID-19 was 11.7 (95% CI, 7.2-18.1) per 10,000 person-months in patients with psoriasis and 14.4 (95% CI, 14.3-14.5) in the general population; the incidence rate of death from COVID-19 was 1.3 (95% CI, 0.2-4.3) and 4.7 (95% CI, 4.6-4.7) in patients with psoriasis and the general population, respectively. The standardized incidence ratio of hospitalization and death in patients with psoriasis compared with those in the general population was 0.94 (95% CI, 0.57-1.45; P = .82) and 0.42 (95% CI, 0.07-1.38; P = .19), respectively. CONCLUSIONS: Our data did not show any adverse impact of biologics on COVID-19 outcome in patients with psoriasis. We would not advise biologic discontinuation in patients on treatment since more than 6 months and not infected with severe acute respiratory syndrome coronavirus 2 to prevent hospitalization and death from COVID-19.