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International Journal of Dermatology Apr 2024Tirbanibulin 1% ointment is approved for the field treatment of Olsen grade I actinic keratoses (AKs) of the face and scalp.
BACKGROUND
Tirbanibulin 1% ointment is approved for the field treatment of Olsen grade I actinic keratoses (AKs) of the face and scalp.
METHODS
We performed a multicenter retrospective study involving 15 dermatologic units in Italy to investigate the efficacy and tolerability of tirbanibulin in a real-life setting. 250 patients were enrolled. Tirbanibulin, 1% ointment, was applied daily for five consecutive days. The efficacy of treatment was measured with modifications of the Actinic Keratosis Area and Severity Index (AKASI). A satisfactory response was defined by complete (100% reduction in the number of lesions) or partial clearance (75-99%) of treated AKs.
RESULTS
Overall, the AKASI score was significantly reduced in the studied population (mean, from 4.1 ± 2.7 to 1.4 ± 1.5; P < 0.001). A satisfactory response was observed in 222 (88.8%) cases. The proportion of satisfactory responses was higher when follow-up was performed after 8 weeks (34/35, 97.1%). The reduction in AKASI was significant in patients with Olsen grade II or III lesions (from 5.3 ± 2.8 to 1.6 ± 1.6; P < 0.001). A satisfactory response was observed in 91/104 (87.5%) cases. AKASI reduction was also significant in patients with trunk or limb AKs (from 7.0 ± 1.3 to 2.0 ± 1.6; P = 0.018) since a satisfactory response was observed in 7/8 (87.5%) cases. Tirbanibulin was well tolerated; all adverse events (AEs) included transient local reactions at the site of treatment. Overall, 231 patients had at least one AE. Only 7 (2.8%) grade 4 AEs were recorded.
CONCLUSION
Our retrospective study confirmed that tirbanibulin 1% ointment is effective and well tolerated in a real-life setting and is also promising for Olsen grade II and grade III AKs and AKs localized on difficult-to-treat areas.
PubMed: 38605473
DOI: 10.1111/ijd.17168 -
ACS Infectious Diseases May 2024Host-acting compounds are emerging as potential alternatives to combating antibiotic resistance. Here, we show that bosutinib, an FDA-approved chemotherapeutic for...
Host-acting compounds are emerging as potential alternatives to combating antibiotic resistance. Here, we show that bosutinib, an FDA-approved chemotherapeutic for treating chronic myelogenous leukemia, does not possess any antibiotic activity but enhances macrophage responses to bacterial infection. In vitro, bosutinib stimulates murine and human macrophages to kill bacteria more effectively. In a murine wound infection with vancomycin-resistant , a single intraperitoneal bosutinib injection or multiple topical applications on the wound reduce the bacterial load by approximately 10-fold, which is abolished by macrophage depletion. Mechanistically, bosutinib stimulates macrophage phagocytosis of bacteria by upregulating surface expression of bacterial uptake markers Dectin-1 and CD14 and promoting actin remodeling. Bosutinib also stimulates bacterial killing by elevating the intracellular levels of reactive oxygen species. Moreover, bosutinib drives NF-κB activation, which protects infected macrophages from dying. Other Src kinase inhibitors such as DMAT and tirbanibulin also upregulate expression of bacterial uptake markers in macrophages and enhance intracellular bacterial killing. Finally, cotreatment with bosutinib and mitoxantrone, another chemotherapeutic in clinical use, results in an additive effect on bacterial clearance in vitro and in vivo. These results show that bosutinib stimulates macrophage clearance of bacterial infections through multiple mechanisms and could be used to boost the host innate immunity to combat drug-resistant bacterial infections.
Topics: Nitriles; Phagocytosis; Animals; Quinolines; Macrophages; Aniline Compounds; Mice; Humans; Enterococcus faecalis; Reactive Oxygen Species; Anti-Bacterial Agents; Mice, Inbred C57BL; NF-kappa B; Cell Survival; Gram-Positive Bacterial Infections
PubMed: 38602352
DOI: 10.1021/acsinfecdis.4c00086 -
Turkish Journal of Pharmaceutical... Mar 2024The primary goal of this study was to create and validate a simple, precise, sensitive, and accurate ultra-performance liquid chromatography (UPLC) method for estimating...
OBJECTIVES
The primary goal of this study was to create and validate a simple, precise, sensitive, and accurate ultra-performance liquid chromatography (UPLC) method for estimating tirbanibulin in pure and dosage form.
MATERIALS AND METHODS
A UPLC technique was developed using a Waters Acquity UPLC Phenyl (100 x 2.1 mm, 1.7 µm) column. The developed technique was validated in accordance with the International Conference on Harmonization (ICH) guidelines.
RESULTS
Tirbanibulin was separated chromatographically with high resolution using the mobile phase acetonitrile: buffer (30:70 ) at 0.5 mL/min, 5 µL injection volume, and 220 nm wavelength. The validated technique was found to be linear in the 1-15 µg/mL range. The detection and quantification limits for tirbanibulin were 0.03 and 0.1 µg/mL, respectively. The percentage relative standard deviation was less than 2%, demonstrating the precision of the developed technique. Furthermore, the recovery rate was nearly 100%, confirming the accuracy of the method. Minor modifications to the chromatographic conditions demonstrated the robustness of the method.
CONCLUSION
The developed analytical method was precise, simple, reproducible, and sensitive. Consequently, it can be used to determine tirbanibulin.
PubMed: 38528791
DOI: 10.4274/tjps.galenos.2023.18124 -
Medicina (Kaunas, Lithuania) Jan 2024: Tirbanibulin 1% ointment is a novel synthetic anti-proliferative agent that inhibits tubulin polymerization. It is approved for treating actinic keratosis (AK) on the...
: 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. : 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). : 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. Our real-life experience confirms the effectiveness and safety of tirbanibulin ointment for the treatment of AKs.
Topics: Adult; Male; Female; Humans; Middle Aged; Aged; Aged, 80 and over; Keratosis, Actinic; Prospective Studies; Ointments; Patient Compliance; Treatment Outcome; Acetamides; Morpholines; Pyridines
PubMed: 38399512
DOI: 10.3390/medicina60020225 -
Pharmaceuticals (Basel, Switzerland) Dec 2023Actinic keratosis is a common precancerous skin lesion that can progress into invasive squamous cell carcinomas. Many topical treatments for actinic keratoses often have...
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 cm 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.
PubMed: 38139813
DOI: 10.3390/ph16121686 -
RSC Advances Nov 2023Tirbanibulin, an FDA-approved microtubule-targeting agent (MTA) introduced in 2020, represents a pioneering treatment for precancerous actinic keratosis. Despite its...
Tirbanibulin, an FDA-approved microtubule-targeting agent (MTA) introduced in 2020, represents a pioneering treatment for precancerous actinic keratosis. Despite its failure to gain approval as an anticancer agent due to insufficient efficacy, there remains potential value in extending its application into malignancy treatment through tirbanibulin-based derivatives. Tirbanibulin possesses a distinctive dual mechanism of action involving microtubule and Src inhibition, distinguishing it from other MTAs. In spite of its unique profile, exploration of tirbanibulin's structure-activity relationship (SAR) and the development of its derivatives are significantly limited in the current literature. This study addresses this gap by synthesizing various tirbanibulin derivatives and exploring their SAR through modifications in the core amide motif and the eastern benzylamine part. Our results underscore the critical role of the pyridinyl acetamide core structure for optimal cellular potency, with favorable tolerance observed for modifications at the position of the benzylamine moiety. Particularly noteworthy is the analogue modified with -fluorine benzylamine, which exhibited favorable PK profiles. These findings provide crucial insights into the potential advancement of tirbanibulin-based compounds as promising anticancer agents.
PubMed: 38077981
DOI: 10.1039/d3ra06790d -
Acta Dermato-venereologica Oct 2023
Topics: Humans; Keratosis, Actinic; Ointments; Retrospective Studies; Treatment Outcome; Upper Extremity
PubMed: 37876333
DOI: 10.2340/actadv.v103.15296 -
JAAD Case Reports Oct 2023
PubMed: 37817888
DOI: 10.1016/j.jdcr.2023.07.005 -
Cancers Aug 2023Skin cancer is an overarching label used to classify a variety of cutaneous malignancies. Surgical excision procedures are the commonly used treatments for these... (Review)
Review
Skin cancer is an overarching label used to classify a variety of cutaneous malignancies. Surgical excision procedures are the commonly used treatments for these lesions; however, the choice to perform operative intervention may be influenced by other factors. Established research and literature suggest that topical treatments limit the need for surgical intervention and its commonly associated adverse effects, including infection and scarring. In addition, the growing indications for the usage of topical therapies in BCC treatment, as well as their increased availability and therapeutic options, allow for their greater applicability in the dermatology clinic. Certain topical therapies have been highlighted in research, especially those targeting basal cell carcinoma (BCC) and actinic keratosis (AK). There is also a clear correlation between cost and treatment outcomes, considering BCC's ever-growing prevalence and the proportion of excised lesions being reported as malignant. This review will discuss BCC and AK lesion criteria that result in the most successful outcomes using topical treatments, then highlight the various topical treatment options, and finally address their clinical significance moving forward.
PubMed: 37568743
DOI: 10.3390/cancers15153927 -
Journal of Clinical Medicine Jul 2023Actinic keratosis (AK) is a cutaneous lesion resulting from the proliferation of atypical epidermal keratinocytes caused by long-term exposure to ultraviolet radiation....
BACKGROUND
Actinic keratosis (AK) is a cutaneous lesion resulting from the proliferation of atypical epidermal keratinocytes caused by long-term exposure to ultraviolet radiation. AK may progress to cutaneous squamous cell carcinoma (cSCC) and therefore is often treated with topical agents such as 5-fluorouracil, diclofenac, imiquimod, and photodynamic therapy. Tirbanibulin has been approved based on two phase III trials in the USA. However, real-world evidence for tirbanibulin is absent.
METHODS
This was a single-centre study of adult patients with clinically typical, visible AK on the face or scalp treated with tirbanibulin 1% ointment. Treatment was administered as per label once daily for 5 consecutive days on the same lesions or field. Treatment outcomes were assessed 4 weeks after treatment, with additional optional assessments conducted at later time points. Efficacy was measured using the actinic keratosis area and severity index (AKASI) and digital dermoscopy.
RESULTS
A total of 33 patients were treated of whom 30 were analysed. The median AKASI score was 5.6 (1.4-11) pre-treatment and 1.2 (0-7.4) post-treatment ( < 0.0001). Complete clearance as defined by AKASI scores less than 1 was achieved in 47% ( = 14) and 57% ( = 13) at the first and second follow-up, respectively. All local reactions resolved spontaneously and without sequelae. The most common local reactions were erythema (80%, = 26) and flaking or scaling (43%, = 13).
CONCLUSIONS
Tirbanibulin 1% ointment significantly and rapidly reduced the AKASI score in a real-world setting. The complete clearance rates were in line with those observed in the two pivotal trials.
PubMed: 37510952
DOI: 10.3390/jcm12144837