Background and Objectives: Tirbanibulin 1% ointment is a novel synthetic anti-proliferative agent that inhibits tubulin polymerization. It is approved for treating actinic keratosis (AK) on the face and scalp in adults. It has demonstrated good efficacy, an adequate safety profile and excellent patient adherence in the phase 3 clinical trials, however data about its real-life efficacy and safety are lacking. Here we report the experience of the dermatology unit of the University Hospital of Messina. Materials and Methods: We performed a spontaneous open-label, prospective non-randomized study to assess the effectiveness and safety of tirbanibulin 1% ointment for the treatment of 228 AKs in 38 consecutive patients—28 males (73%) and 10 females (26%)—aged between 52 and 92 years (mean age: 72 ± 8.92 years). Results: Total clearance was recorded in 51% of lesions, while partial clearance was recorded in 73% of lesions. An excellent tolerability profile and high compliance rate were observed, with no treatment discontinuation due to the onset of adverse events. Conclusion: Our real-life experience confirms the effectiveness and safety of tirbanibulin ointment for the treatment of AKs.

Introduction: The discovery of serine protease proprotein convertase subtilisin-kexin type 9 (PCSK9) has revolutionized pharmacological lipid-lowering treatments. The first PCSK9 antagonists (PCSK9-A), evolocumab and alirocumab, were approved in 2015. Targeting PCSK9 synthesis marked a major advancement in this field, leading to the development of inclisiran, a long-acting siRNA targeting PCSK9 mRNA. However, real-world safety data on this drug are still limited. Therefore, this study aims to provide a real-world safety evaluation of inclisiran, comparing its characteristics to those of PCSK9-As. Methods: A retrospective pharmacovigilance study was conducted using EudraVigilance (EV). Inclisiran-related individual case safety reports (I-ICSRs) from 01/01/2021 to 06/30/2023 were retrieved. ICSRs for evolocumab or alirocumab from 01/01/2015 to 06/30/2023 were collected as a reference group (RG). ADRs were classified using the MedDRA dictionary. Data were evaluated using descriptive and disproportionality analyses. Crude reporting odds ratio (ROR) with 95% confidence intervals (CI) were used as disproportionality measures. Results: Of the 15,236 ICSRs, 3.7% (n = 563) involved inclisiran, with the rest in the RG. Most I-ICSRs involved female patients (51.7%) aged 18 to 64 (52.8%). The most-reported ADRs for inclisiran were “general disorders and administration site conditions” (n = 347) and “investigations” (n = 277). Significant disproportionality was found in I-ICSRs compared to the RG for “Myalgia” (ROR: 2.43; 95% CI: 1.94–3.04), “Low-density lipoprotein increased” (ROR: 11.95; 95% CI: 9.10–15.52), and “Drug ineffective” (ROR: 6.37; 95% CI: 4.64–8.74). Conclusions: The inclisiran safety profile aligns with the existing literature and pre-commercial data. However, further studies are needed to fully understand the observed differences with PCSK9-As.

Background: Tirbanibulin 1% ointment has demonstrated short-term efficacy and excellent tolerability in the treatment of actinic keratosis (AK) on the face and scalp. However, data on long-term efficacy are still lacking. Materials and Methods: This prospective, single-center, 12-month extension study included patients with facial and scalp AKs previously treated with tirbanibulin 1% ointment once daily for 5 consecutive days. Long-term analysis was restricted to lesions that had achieved complete clinical and dermoscopic clearance at the 2-month follow-up. At 12 months, the treated areas were reassessed clinically and dermoscopically. High-resolution images obtained at baseline, 2 months, and 12 months were compared lesion by lesion to distinguish sustained clearance, recurrence at the same anatomical site, and the development of new AKs within the treated field. Results: Thirty-seven patients were reassessed at 12 months. Of the 228 AKs treated at baseline, 116 lesions had achieved complete clearance at 2 months and were therefore eligible for long-term evaluation. At 1 year, 70/116 lesions (60.3%) remained free of recurrence, whereas 46/116 (39.7%) relapsed. Sustained clearance was observed in 35/51 grade 1 lesions (68.6%), 32/57 grade 2 lesions (56.1%), and 3/8 grade 3 lesions (37.5%). In addition, 35 new AKs developed within the previously treated field. No delayed local or systemic adverse events and no progression to invasive cSCC were observed during follow-up. Patient-reported satisfaction was high, and 94% of patients stated they would be willing to repeat the treatment. Conclusions: Tirbanibulin was associated with sustained lesion clearance at one year, particularly in lower-grade AKs. While recurrence remains relatively common—especially in thicker lesions—the treatment was well tolerated and associated with no delayed adverse effects. Its short application regimen and excellent safety profile support tirbanibulin’s role in the long-term management of field cancerization.