Risankizumab as a Therapeutic Approach for Recalcitrant Pyoderma Gangrenosum.

ABSTRACT: Pyoderma gangrenosum (PG) is a neutrophilic dermatosis that is challenging to diagnose and treat. Clinicians frequently use fast-acting corticosteroids, which are subsequently combined with slower-acting immunosuppressants to progressively taper the corticosteroid dosage. Current research is focused on the use of monoclonal antibodies (mAbs) directed against target molecules involved in the pathogenesis of PG. However, available data on their efficacy are based on sporadic case reports and clinical experiences, so the authors aimed to evaluate the efficacy of risankizumab, an anti-interleukin-23 mAb, in the management of two complex PG cases. The authors enrolled two patients with PG who were already treated with immunosuppressive therapies. Their management was based on the off-label use of an mAb directed against the p19 subunit of interleukin-23: risankizumab. Patients received subcutaneous injections of 150 mg at the start of treatment, at week 4, and then every 10 weeks thereafter. Systemic therapy was combined with local management of ulcers, based on the principles of TIME (tissue, infection, moisture balance, and epithelialization) applied to the inflammatory and noninflammatory phases of PG. Clinical resolution was obtained at week 24 for patient 1 and week 16 for patient 2 and was maintained until week 40, without adverse effects or disease recurrence. These clinical cases demonstrate that risankizumab is a valid tool in terms of efficacy and safety for complicated cases of multirefractory PG when provided in parallel with local personalized wound management.

Assessment and Monitoring of Nail Psoriasis with Ultra-High Frequency Ultrasound: Preliminary Results.

Psoriatic onychopathy is one of the clinical presentations of psoriasis and a well-known risk factor for the development of psoriatic arthritis. High-frequency ultrasounds (HFUS > 20 MHz) have recently been used to evaluate the nail apparatus of healthy and psoriatic subjects. The aim of our study was to detect by means of ultra-high-frequency ultrasound (UHFUS 70-100 MHz) alterations of the nail bed and matrix in patients with psoriatic onychopathy and to monitor these parameters during the treatment with monoclonal antibody (mAb). We enrolled 10 patients with psoriatic onychopathy and naive to previous biologic therapies. Patients were evaluated at baseline, after 1 month and after 3 months from the beginning of mAb therapy by a complete clinical assessment and US evaluation. A UHFUS examination with a 70 MHz probe was performed on the thumbnail (I), the index fingernail (II) and the nail with greater clinical impairment (W). The following measurements were analyzed: nail plate thickness (A), nail bed thickness (B), nail insertion length (C), nail matrix length (D) and nail matrix thickness (E). Among the various parameters analyzed, some measures showed a statistically significant decrease with p-value < 0.05 (t0 WA = 0.52 mm vs. t2 WA = 0.42 mm; t0 WB = 2.8 mm vs. t2 WB = 2.4 mm; t0 WE = 0.76 mm vs. t2 WE = 0.64 mm; t0 IIA = 0.49 mm vs. t2 IIA = 0.39 mm). In conclusion, UHFUS could represent a viable imaging technique for the real-time evaluation and monitoring of psoriatic onychopathy, thus supporting the clinical parameters and revealing any subclinical signs of early drug response.

An Integrated Systemic and Local Wound Management in Recalcitrant Pyoderma Gangrenosum.

Pyoderma gangrenosum (PG) is a neutrophilic inflammatory dermatosis, whose management still represents a clinical challenge due to frequent unresponsive cases. The aim of our study was to evaluate the efficacy of a novel, combined approach including local wound management, based on the principle of PG-TIME and a systemic therapy with an anti interleukin (IL)-17A monoclonal antibody (mAb). We presented a case of a 37-year-old female patient, affected by multi-refractory PG. The patient was treated with a combined approach of both local and systemic therapy. Wound clinical improvement was assessed by Wound Bed Score (WBS), wound size was evaluated through 3D camera laser scanner, and pain was evaluated with visual analog scale (VAS). After 52 weeks of therapy, the association of local wound management with ixekizumab 80 mg [160 mg at time (T) 0; 80 mg every 2 weeks until week 12; 80 mg every 4 weeks] allowed us to perform skin grafting and obtain complete wound healing. Our clinical case demonstrated the efficacy of a novel combination therapy for the treatment of recalcitrant PG based on IL-17 mAbs and local wound management built on the main features of PG-TIME.

Tuscany consensus for the treatment of moderate-severe psoriasis: update and focus on practical guidelines for place in therapy of anti-IL-17 and anti-IL-23 biologics.

Psoriasis is a common chronic skin disease characterized by a worldwide distribution and a natural tendency towards progression. According to the many clinical forms, the extension of the disease and the many comorbidities, almost the 20% of the patients require a systemic treatment. Biologics have greatly changed the ongoing of psoriasis and the quality of life of psoriasis patients. After the anti-TNF-alpha, which were the first biologics in use for psoriasis, the improvement in knowledge of the pathogenetic mechanisms underlying the disease has led to the development of a series of more specific therapies for psoriasis. This "second generation" of biologics includes the interleukin (IL)-12/23 inhibitor ustekinumab, IL-17 inhibitors (secukinumab and ixekizumab), the IL-17 receptor A (IL-17RA) antagonist brodalumab, and the IL-23 inhibitors guselkumab, risankizumab and tildrakizumab. This study represents an update of the Tuscany consensus focused on the use of new drugs, such as anti-IL-17 and anti-IL-23 in moderate-to-severe psoriasis and their correct place in therapy according to specific clinical requests and in full respect of the current financial restrictions.

Impact of psychiatric comorbidities in psoriasis, hidradenitis suppurativa and atopic dermatitis: The importance of a psychodermatological approach.

BACKGROUND: There is a strong interaction between the immunological and nervous system in the skin. Lesions that are physically disfiguring and chronically relapsing have a high impact on quality of life (QoL) and can result in the emergence of psychiatric disorders. The literature data confirm a higher prevalence of psychiatric disorders in patients with psoriasis, hidradenitis suppurativa (HS) and atopic dermatitis (AD), but such data are compromised by low-quality evidence due to methodological heterogeneity. OBJECTIVES: The primary aim was to analyse the prevalence of psychiatric comorbidities in a group of psoriasis, AD and HS patients compared with a control group. The secondary aims were to evaluate the impact of psychiatric comorbidities on the disease development, severity, flare-ups and QoL. METHODS: A total of 59 cases and 64 controls were included. RESULTS: Generalized anxiety disorder and depressive disorder with anxious distress were found to be risk factors for AD. Age, smoking and substance-related disorder showed a specific association with HS. Major depressive disorder showed a specific association with dermatology life quality index (DLQI) and all the above disease flare-ups. CONCLUSIONS: Atopic dermatitis, psoriasis and HS are associated with psychiatric disorders. A psychodermatological approach improves outcomes in terms of QoL, disease flare-ups and long-term management.

A real-life experience as a proof of Guselkumab effectiveness and safety in patients with moderate to severe psoriasis.

Psoriasis is a skin disorder characterized by chronic inflammation driven by different immunologic pathways, among which the IL-23/Th17 axis plays a pivotal role. For this reason, the use of IL23p19 inhibitors in psoriasis treatment has been evaluated over the years. Guselkumab, a totally human IgG1 lambda monoclonal antibody, that selectively blocks the p 19 subunit of IL- 23 has demonstrated high efficacy and safety throughout several, randomized, double-blind phase III trials (VOYAGE 1 and 2, NAVIGATE and ECLIPSE). We designed a single-center retrospective cohort study in a population consisting of 46 patients followed from December 2018 to April 2021. After a diagnosis of moderate to severe psoriasis, all the patients were considered suitable to receive treatment with Guselkumab. In our population, among those who achieved clinical improvement in terms of Psoriasis Area Severity Index (PASI), PASI 75, 90, and 100 were achieved on average on weeks 14, 19, 21 respectively. We then analyzed a subgroup of our population, consisting of 35 patients, who had an identical follow-up time of 28 weeks, thus observing the trend in mean PASI at subsequent assessments and the number of patients who had reached PASI 75, PASI 90, and PASI 100 at week 4 (10; 3; 1), week 12 (12; 13; 11), week 20 (7; 6; 2), and week 28 (1; 4; 6), respectively. The results obtained are in line with those obtained from previous studies, thus confirming that Guselkumab is an excellent choice in terms of security, long-term efficacy, and overall tolerance.

Unusual presentation of angiolymphoid hyperplasia with eosinophilia treated with intralesional and topic corticosteroid combination therapy.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon angioproliferative benign disorder. A 24- year-old Caucasian female patient presented with multiple itchy reddish pearly nodule.

Ultra-high-frequency ultrasound monitoring of plaque psoriasis during ixekizumab treatment.

BACKGROUND: High-frequency ultrasound (HFUS) is a non-invasive method that detects superficial skin features. Ultra-high frequencies (50-100 MHz) can reveal epidermis and dermis structures. OBJECTIVES: In this study, we describe the psoriatic plaque using a new device equipped with a 70 MHz probe (VEVO® MD, Fujifilm, VisualSonics) and we assess the lesion before and after ixekizumab. METHODS: We examined the superficial hyperechoic band, the subepidermal hypoechoic band (SLEB), and the vascularization of the plaque in ten patients affected by plaque psoriasis. RESULTS: The average superficial hyperechoic band thickness was 0.2157 mm before treatment, 0.1611 mm after 15 days, and 0.1354 mm (P < .05) after 30 days. The SLEB thickness was 0.7535 mm at baseline, 0.3300 mm after 15 days (P < .05), and 0.2007 mm (P < .05) after 30 days. The average percentage vascularization was 50.21% at baseline, 13.15% after 15 days (P < .05), and 5.97% after 30 days. UHFUS assessment highlighted the rapid action of the drug in terms of the decrease in vascularization after 15 days. It revealed a statistically significant reduction in SLEB thickness after 15 days and a significant reduction in the hyperechoic superficial band after 30 days. CONCLUSIONS: VEVO® MD provides physicians with high-resolution details of the psoriatic plaque, thus enabling tailored-made treatments.

Secukinumab demonstrates improvements in absolute and relative psoriasis area severity indices in moderate-to-severe plaque psoriasis: results from a European, multicentric, retrospective, real-world study.

Objective: This European, multicentric, retrospective study aimed to collect data on secukinumab effectiveness in a real-world setting.Research design and methods: All psoriatic patients starting secukinumab between January 2016 and February 2017 in 11 European centers were followed until February 2018 and retrospectively evaluated.Main outcome measures: Secukinumab effectiveness was assessed by relative improvement from baseline of the Psoriasis Area Severity Index (PASI) and absolute PASI score modifications throughout 52 weeks of therapy. Additionally measures assessing effectiveness were used, including improvements of body surface area (BSA) and Dermatology Life Quality Index (DLQI).Results: Out of the 330 patients with potentially 52-week treatment duration, naïve to biologics patients showed greater probability to achieve PASI score of ≤1, ≤2, ≤3, and ≤5 at week 12, compared to bio-experienced patients (45.86% vs. 27.17%, 62.42% vs. 42.42%, 73.89% vs. 57.80%, and 84.08% vs. 74.57%, respectively). The greater effectiveness of secukinumab treatment in bio-naïve patients was confirmed at week 24 and 52.Conclusions: In this real-world experience, secukinumab was proven effective in treating psoriasis patients throughout a 52-weeks observation period, with higher response in bio-naïve patients. This study may contribute to defining the clinical profile of secukinumab best-responders.

Switching from Secukinumab to Ustekinumab in Psoriasis Patients: Results from a Multicenter Experience.

BACKGROUND: Switching between biologics is commonly performed for the management of plaque psoriasis. However, no evidence about switching from secukinumab to ustekinumab has been reported. METHODS: This retrospective observational multicenter study aimed to describe efficacy and safety of ustekinumab in secukinumab nonresponder patients. RESULTS: A total of 21 patients unresponsive to secukinumab were treated with ustekinumab for a mean period of 53.3 weeks. Ustekinumab was effective in reducing disease severity, with significant improvements of both psoriasis area severity index (PASI) and dermatology quality of life index (DLQI) scores. PASI score improvements of 31.8, 44, 77.8, 80.3, 80.5, and 89.6%, at week 4, 12, 24, 36, 48, and above 60 weeks, respectively, were detected (p < 0.05), achieving PASI 50, 75, and > 90 responses in 93.8, 87.5, and 50% of patients at week 48. Four patients withdrew from ustekinumab treatment because of inefficacy, and failure of multiple biologic agents (> 2) seemed to affect ustekinumab drug survival. No serious adverse events (AEs) were reported while 38.1% of patients experienced mild AEs. CONCLUSION: Ustekinumab was safe and effective in treating patients unresponsive to secukinumab.