From In Silico Simulation between TGF-β Receptors and Quercetin to Clinical Insight of a Medical Device Containing Allium cepa: Its Efficacy and Tolerability on Post-Surgical Scars

1) objective: keloid and hypertrophic scars are a challenge in clinical management, causing functional and psychological discomfort. these pathological scars are caused by a proliferation of dermal tissue following skin injury. the TGF-beta/smad signal pathway in the fibroblasts and myofibroblasts is involved in the scarring process of skin fibrosis. today, multiple therapeutic strategies that target the TGF-beta/smad signal pathway are evaluated to attenuate aberrant skin scars that are sometimes difficult to manage. we performed a head-to-head, randomized controlled trial evaluating the appearance of the post-surgical scars of 64 subjects after two times daily topical application to compare the effect of a class I pullulan-based medical device containing allium cepa extract 5% and hyaluronic acid 5% gel versus a class I medical device silicone gel on new post-surgical wounds. (2) methods: objective scar assessment using the vancouver scar scale (VSS), POSAS, and other scales were performed after 4, 8, and 12 weeks of treatment and statistical analyses were performed. the trial was registered in clinical trials.gov ( NCT05412745). In parallel, molecular docking simulations have been performed to investigate the role of allium cepa in TGF-beta/smad signal pathway. (3) results: we showed that VSS, POSAS scale, itching, and redness reduced significantly at week 4 and 8 in the subjects using devices containing allium cepa and HA. no statistically significant differences in evaluated scores were noted at 12 weeks of treatment. safety was also evaluated by gathering adverse events related to the application of the gel. subject compliance and safety with the assigned gel were similar between the two study groups. molecular docking simulations have shown how allium cepa could inhibit fibroblasts proliferation and contraction via TGF- beta/smad signal pathway. (4) conclusions: the topical application of a pullulan-based medical device containing allium cepa and HA showed a clear reduction in the local inflammation, which might lead to a reduced probability of developing hypertrophic scars or keloids

Preliminary Evidence of Efficacy, Safety, and Treatment Satisfaction with Tirbanibulin 1% Ointment: A Clinical Perspective on Actinic Keratoses

background: actinic keratosis is a common precancerous skin lesion that can progress into invasive squamous cell carcinomas. many topical treatments for actinic keratoses often have poor tolerability and prolonged duration. Tirbanibulin is a novel synthetic drug with potent antitumor and antiproliferative activities. methods: we conducted a single-center, prospective and observational study using tirbanibulin ointment on a 25 cm2 area for 5 consecutive days on 30 participants with AKs on the face or scalp. They were followed for at least 57 days to assess the safety profile and efficacy of the drug as well as treatment satisfaction. we evaluated six signs of local skin reaction (LSR): erythema, scaling, crusting, swelling, blisters/pustules, and erosions/ulcerations, grading the severity as mild, moderate, or severe. The effectiveness was evaluated both clinically and dermoscopically. the treatment satisfaction was assessed using the treatment satisfaction questionnaire for medication (TSQM 1.4). results: on day 57, 70% of the patients showed a complete clinical and dermoscopic response. The highest scores obtained from the TSQM 1.4 were more evident in the convenience and side effects domains. most LSRs, including erythema (83.3%), scaling (30%), and swelling (3.3%), occurred on day 8 but resolved spontaneously. Conclusion: Tirbanibulin is a viable therapeutic option with a short regimen treatment and good tolerability, which favors therapy adherence

Efficacy of Tildrakizumab for the Treatment of Difficult-to-Treat Areas: Scalp, Nail, Palmoplantar and Genital Psoriasis

Tildrakizumab, an IL-23 inhibitor, is effective and safe for the improvement of moderate-to-severe chronic plaque psoriasis. However, little evidence is available on the use of this biologic in psoriasis in difficult-to-treat locations. In this retrospective analysis, we treated patients with 100 mg tildrakizumab at Day 0, after 4 weeks and every 12 weeks thereafter. Disease severity and treatment response was assessed by the Psoriasis Area and Severity Index (PASI), the static Physician's Global Assessment of Genitalia (sPGA-G), the Psoriasis Scalp Severity Index (PSSI), Nail Psoriasis Severity Index (NAPSI) and the Palmoplantar Psoriasis Area and Severity Index (ppPASI) at baseline and after 4, 12 and 28 weeks. We followed 18 patients (mean age 49.1 +/- 12.7 years, 61.1% male) with psoriasis localized to the genital region (N = 7), scalp (N = 6), nails (N = 5) and palmar/plantar areas (N = 7). PASI score decreased from 11.5 at baseline to 3.1 and 2.4 at 12 and 28 weeks. Tildrakizumab treatment decreased sPGA-G (3.3 to 0.2), PSSI (36.2 to 2.7), NAPSI (48.4 to 15.7) and ppPASI (5.3 to 0) from baseline to 28 weeks, respectively. Data from this real-life retrospective analysis shows that tildrakizumab is an effective option for the management of psoriasis in difficult-to-treat areas

Early clinical response to 5-fluorouracil 0.5% and salicylic acid 10% topical solution in the treatment of actinic keratoses of the head: an observational study

Background Actinic keratosis is one of the most common dermatological disorders. A new topical solution, constituted by 0.5% 5-fluorouracil and 10% salicylic acid (Actikerall, Almirall) has been introduced in the treatment pipeline of hyperkeratotic actinic keratoses of the head and neck. Patients and methods We analyzed in an observational prospective clinical study the short-term treatment effectiveness of 5-fluorouracil and salicylic acid on face and scalp actinic keratoses of grade 1 and 2 of 40 patients. Efficacy assessment was performed by clinical dermatological examination, collecting color photographs, calculating AKASI score, and by means of dermoscopy for each target lesion at every visit. Results AKASI score decreased from an initial score of 3.3 to a final score of 0.9. At week 4, we were able to record a complete clearance of 50% of the treated lesions and a partial clearance of 28%. At the end of 12 weeks, 84% of the total lesions showed complete clearance, while 8% had partial clearance. Conclusions 5-fluorouracil and salicylic acid topical solution is effective in the treatment of mild to moderate actinic keratoses. In the future, further studies are needed to evaluate the chance of adjusting drug dosage according to patients' and actinic keratoses features

A Real-Life Study on the Use of Tildrakizumab in Psoriatic Patients

Tildrakizumab is a humanized IgG1κ monoclonal antibody that selectively targets the p19 subunit of interleukin IL-23, thereby inhibiting the IL-23/IL-17 axis, which is primarily implicated in the immunopathogenesis of psoriasis. Tildrakizumab is approved for the treatment of moderate-to-severe plaque-type psoriasis in adults based on the evidence of two randomized and controlled phase-III clinical trials (reSURFACE 1 and reSURFACE 2). Here, we report our real-life experience treating 53 psoriatic patients (19 female and 34 male) who were administered tildrakizumab every 12 weeks and received follow-ups over 52 weeks. Descriptive and inferential statistical analyses were performed, in particular the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI) and, if applicable, the Nail Psoriasis Severity Index (NAPSI) and Palmoplantar Psoriasis Physician Global Assessment (PPPGA). These were assessed at baseline and after different timepoints (weeks) during the follow-up period. We described and evaluated demographical and epidemiological characteristics in our cohort group, focusing on comorbidities. In this group, 35.9% of patients were female and 64.1% were male, with 47.1% being smokers and with a mean age of 51.2 years. A total of 37.7% of these patients was affected by scalp psoriasis; regarding comorbidities, hypertension was the most frequent (32.5%), followed by psoriatic arthritis (PsA) (18.60%) and diabetes (13.9%). At week 52, 93%, 90.2% and 77% of patients achieved a PASI reduction ≥75% (PASI 75), PASI 90 and PASI 100, respectively. In addition, NAPSI, PPPGA and DLQI scores were significantly reduced by week 52. In our cohort of complex psoriasis patients, disease remission began at the end of the fourth week of treatment and remained constant from week 16 to week 52

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

AbstractPurpose 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

Fast Clinical Response of Bimekizumab in Nail Psoriasis: A Retrospective Multicenter 36-Week Real-Life Study

(1) Background/Objectives: Nail psoriasis (NP) is a chronic and difficult-to-treat disease, which causes significant social stigma and impairs the patients’ quality of life. Moreover, nail psoriasis is a true therapeutic challenge for clinicians. The presence of nail psoriasis can be part of a severe form of psoriasis and can have predictive value for the development of psoriatic arthritis. Our real-world-evidence multicenter study aims to evaluate the efficacy of bimekizumab in nail psoriasis. (2) Methods: A retrospective analysis of a multicenter observational study included 834 patients affected by moderate-to-severe psoriasis, in 33 Dermatologic Units in Italy, treated with bimekizumab from December 2022 to September 2023. Clinimetric assessments were based on Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and Physician’s Global Assessment of Fingernail Psoriasis (PGA-F) for the severity of nail psoriasis at 0, 12, 24, and 36 weeks. (3) Results: Psoriatic nail involvement was present in 27.95% of patients. The percentage of patients who achieved a complete clearance of NP in terms of PGA-F 0 was 31.7%, 57%, and 88.5% at week 4, 16, and 36, respectively. PASI 100 was achieved by 32.03% of patients at week 4, by 61.8% at week 16, and by 78.92% of patients at week 36. The mean baseline PASI was 16.24. The mean DLQI values for the entire group of patients at baseline, at week 4, at week 16, and at week 36 were 14.62, 3.02, 0.83, and 0.5, respectively. (4) Conclusions: Therapies that promote the healing of both the skin and nails in a short time can also ensure a lower risk of subsequently developing arthritis which is disabling over time. Bimekizumab proved to be particularly effective to treat NP, with a fast response in terms of complete clearance, with over 88.5% of patients free from NP after 36 weeks. The findings of our real-world study showed that patients with moderate-to-severe PsO and concomitant NP had significantly faster and more substantial improvements in NP up to 36 weeks with respect to previous research findings. Considering the rapid healing of the nail, the dual inhibition of IL17 A and F might have a great value in re-establishing the dysregulation of keratin 17 at the nail level