Factors influencing response to ingenol mebutate therapy for actinic keratosis of face and scalp

Skroza, Nevena; Proietti, Ilaria; Bernardini, Nicoletta; Balduzzi, Veronica; Mambrin, Alessandra; Tolino, Ersilia; Zuber, Sara; Torre, Giuseppe La; Potenza, Concetta

doi:10.5306/wjco.v8.i5.405

Cited by 8 publications

(9 citation statements)

References 21 publications

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“…The levels and values of the LSR composite scores obtained were not associated to the treatment efficacy. These results are in accordance with previous research [37,38].…”

Section: Plos Onesupporting

confidence: 94%

Identification of differentially expressed genes in actinic keratosis samples treated with ingenol mebutate gel

Segura¹,

Gadea²,

Nonell³

et al. 2020

PLoS ONE

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Actinic keratosis is a common skin disease that may progress to invasive squamous cell carcinoma if left untreated. Ingenol mebutate has demonstrated efficacy in field treatment of actinic keratosis. However, molecular mechanisms on ingenol mebutate response are not yet fully understood. In this study, we evaluated the gene expression profiles of actinic keratosis lesions before and after treatment with ingenol mebutate using microarray technology. Actinic keratoses on face/scalp of 15 immunocompetent patients were identified and evaluated after treatment with topical ingenol mebutate gel 0.015%, applied once daily for 3 consecutive days. Diagnostic and clearance of lesions was determined by clinical, dermoscopic, and reflectance confocal microscopy criteria. Lesional and non-lesional skin biopsies were subjected to gene expression analysis profiled by Affymetrix microarray. Differentially expressed genes were identified, and enrichment analyses were performed using STRING database. At 8 weeks post-treatment, 60% of patients responded to ingenol mebutate therapy, achieving complete clearance in 40% of cases. A total of 128 differentially expressed genes were identified following treatment, and downregulated genes (114 of 128) revealed changes in pathways important to epidermal development, keratinocyte differentiation and cornification. In responder patients, 388 downregulated genes (of 450 differentially expressed genes) were also involved in development/differentiation of the epidermis, and immune system-related pathways, such as cytokine and interleukin signaling. Cluster analysis revealed two relevant clusters showing upregulated profile patterns in pre-treatment actinic keratoses of responders, as compared to non-responders. Again, differentially expressed genes were mainly associated with cornification, keratinization and keratinocyte differentiation. Overall, the present study provides insight into the gene expression profile of actinic keratoses after treatment with ingenol mebutate, as well as identification of genetic signatures that could predict treatment response.

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“…The levels and values of the LSR composite scores obtained were not associated to the treatment efficacy. These results are in accordance with previous research [37,38].…”

Section: Plos Onesupporting

confidence: 94%

Identification of differentially expressed genes in actinic keratosis samples treated with ingenol mebutate gel

Segura¹,

Gadea²,

Nonell³

et al. 2020

PLoS ONE

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“…Interestingly, the lesion complete response rate for face (mainly forehead) (65%) was slightly higher than for the scalp (58%), possibly because self‐application is more difficult for the scalp than the face. However, a better complete response for AK on the face compared to scalp was also previously observed when MAL DL‐PDT was applied in a clinical setting without self‐application, and also with other AK treatments, such as 5‐fluorouracil and ingenol mebutate …”

Section: Discussionsupporting

confidence: 54%

“…However, a better complete response for AK on the face compared to scalp was also previously observed when MAL DL-PDT was applied in a clinical setting without selfapplication, 19,20 and also with other AK treatments, such as 5fluorouracil 21 and ingenol mebutate. 22,23 As in the previous randomized controlled trial performed in Europe, 10 the most frequent related adverse events (mostly mild erythema, pain and skin burning sensation) were associated with the PDT mode of action. Although mild procedural pain was reported for 30% of patients, some were very mild pain since 86% of patients indicated a score of ≤2 on a 0-10 NRS scale.…”

Section: Discussionmentioning

confidence: 66%

Methyl aminolevulinate daylight photodynamic therapy applied at home for non‐hyperkeratotic actinic keratosis of the face or scalp: an open, interventional study conducted in Germany

Karrer

Aschoff

Dominicus³

et al. 2019

Acad Dermatol Venereol

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Background The efficacy and safety of methyl aminolevulinate daylight photodynamic therapy (MAL DL-PDT) for actinic keratosis (AK) treatment has previously been demonstrated in several studies.Objective To evaluate patient-reported outcomes, effectiveness and tolerability of patient self-applied MAL DL-PDT. Patients and methodsAn open study was conducted in Germany in patients with thin or non-hyperkeratotic and non-pigmented AK. At baseline, the investigator delimited the target anatomical area and skin preparation was discretionary. On day 1, the patient performed MAL DL-PDT at home, in accordance with instructions (after applying sunscreen and skin preparation by abrasive pad). Patient questionnaires were completed on day 1 and 3 months post-treatment.Effectiveness was assessed by investigator at 3 months. Pain and adverse events (AE) were recorded.Results Patients (n = 50) were mostly elderly (mean age: 73.4 years) men (86%). After treatment on day 1, 94% of patients were overall satisfied or very satisfied with the treatment and 98% found the instructions convenient. At 3 months, most patients were satisfied or very satisfied with treatment effectiveness (88%) and aspect of their skin (80%). At 3 months, 62% of overall lesions were completely clear. The main related AEs were mild and expected (erythema, procedural pain and skin burning sensation).Conclusions Patient self-application of MAL DL-PDT resulted in high levels of patient satisfaction, effectiveness and tolerability.

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“…Considering reported data, ingenol mebutate treatment seems to be more effective on the face than on the scalp and the efficacy seems to be directly related to the level of LSR. 50 …”

Section: Review Of Literaturementioning

confidence: 99%

Clinical utility of ingenol mebutate in the management of actinic keratosis: perspectives from clinical practice

Skroza¹,

Bernardini²,

Proietti³

et al. 2018

TCRM

Self Cite

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Actinic keratoses (AKs) are epidermal cutaneous neoplasia observed predominantly in middle-aged and older subjects with mainly photo type I and photo type II on sun-exposed surfaces as a result of DNA damage. AKs have historically been characterized as being “precancerous”; however, now it is considered by many authors a carcinoma in situ that can persist or progress to invasive squamous cell carcinoma (SCC) with metastatic potential. Despite the advances in the recognition of typical clinic, dermoscopic and histologic patterns, currently it is not yet possible to predict which AKs will progress to SCC. For this reason, early diagnosis and effective therapy are recommended based on cost/risk/benefit analysis. Current treatment consists of lesion-directed or field-directed therapies or a combination of both. Among the topical field therapies, ingenol mebutate stands out for its therapeutic efficacy, both as directed lesion therapy and as field directed therapy. The aim of this review is to demonstrate the utility of ingenol mebutate in the management of AK in daily clinical practice and to highlight data from real world in order to confirm evidence from pivotal studies. In order to explore clinical data from real world, PubMed searches were performed with the search terms “clinical data ingenol mebutate” and “real world ingenol mebutate”. The hits were examined for relevant articles using defaults criteria. The timeframe for the sample search started from the first publication on this topic in 2008 up to now. A total of 23 articles were found using the keywords specified above. The overview points out a low number of real-life studies on the effectiveness and tolerability of this novel treatment due to short period of clinical experience for its recent approval. Further real-life studies are required in order to better identify the efficacy, safety and adherence of the drug on a larger population.

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Factors influencing response to ingenol mebutate therapy for actinic keratosis of face and scalp

Cited by 8 publications

References 21 publications

Identification of differentially expressed genes in actinic keratosis samples treated with ingenol mebutate gel

Identification of differentially expressed genes in actinic keratosis samples treated with ingenol mebutate gel

Methyl aminolevulinate daylight photodynamic therapy applied at home for non‐hyperkeratotic actinic keratosis of the face or scalp: an open, interventional study conducted in Germany

Clinical utility of ingenol mebutate in the management of actinic keratosis: perspectives from clinical practice

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