Original article
Ingenol mebutate gel for actinic keratosis: The link between quality of life, treatment satisfaction, and clinical outcomes

https://doi.org/10.1016/j.jaad.2015.01.036Get rights and content

Background

Actinic keratosis therapy can elicit unsightly and painful local skin responses; assessment of treatment satisfaction and health-related quality of life (QoL) is important. Ingenol mebutate gel is a novel topical field therapy for actinic keratosis.

Objective

Post-hoc analyses were performed based on patient-reported outcomes from phase-III trials (n = 1005) to assess the effects of ingenol mebutate on QoL and the relationship between both QoL and treatment satisfaction, and degree of lesion clearance.

Methods

Patients received ingenol mebutate or vehicle for self-application to a 25-cm2 contiguous area: 0.015% once daily for 3 consecutive days (face/scalp) or 0.05% once daily for 2 consecutive days (trunk/extremities). QoL (Skindex-16) and Treatment Satisfaction Questionnaire for Medication data were recorded.

Results

Significant, positive associations between Treatment Satisfaction Questionnaire for Medication score and degree of clearance were identified for patients in the face/scalp (effectiveness P < .0001 and global satisfaction P = .0002) and trunk/extremities (P < .0001 and P = .0014, respectively) groups. There was a significant association between Skindex-16 score and clearance for patients in the face/scalp group for change in symptoms (P = .0218), emotions (P = .0002), and overall Skindex-16 score (P = .0006) from baseline.

Limitations

Clinical trial population findings may not be generalizable to clinical practice.

Conclusion

Ingenol mebutate significantly improved patients' QoL and treatment satisfaction. Improvements were associated with higher degrees of actinic keratosis lesion clearance.

Section snippets

Patient population

Patients were aged 18 years or older and had 4 to 8 clinically typical, visible, discrete AKs within a contiguous 25-cm2 area on the face, scalp, trunk, or extremities. Inclusion and exclusion criteria have been published previously.18 Participating center ethical review boards approved each study, and patients provided written informed consent and allowed photographs of the selected treatment area to be taken.

Trial designs

Four phase-III multicenter, randomized, double-blind, vehicle-controlled trials were

Patient characteristics

Overall, 1005 patients were randomized (ingenol mebutate n = 277 and vehicle n = 270 for face/scalp; ingenol mebutate n = 226 and vehicle n = 232 for trunk/extremities). Patient baseline characteristics and disposition have been reported previously.18

TSQM/Skindex-16 results

Overall, completion rates were high (91.6%-98.9%) for both questionnaires. Patients treated with ingenol mebutate in the face/scalp group and the trunk/extremities group reported significantly greater satisfaction with effectiveness and global

Discussion

Ingenol mebutate therapy significantly improved QoL and treatment satisfaction in phase-III trials. Improvements from baseline were greatest for the emotions domain in Skindex-16. Greater improvements were reported in the face/scalp than for the trunk/extremities group for the emotions and symptoms domains, which reflect the higher efficacy rates for ingenol mebutate on the face/scalp compared with other locations. The results confirm reports of treatment-related improvements in QoL in patients

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      Citation Excerpt :

      Actinic keratoses (AKs) are the most common pre-malignancies of the skin. They cause disfigurement, pain and loss of quality of life [1–5]. If left untreated they may evolve into squamous cell carcinoma and is therefore most often treated [6].

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    These studies (PEP005-014; PEP005-016; PEP005-025; PEP005-028) were funded by Peplin Operations Pty Ltd (subsequently acquired by LEO Pharma A/S).

    Disclosure: Dr Augustin has served as a consultant and investigator for LEO Pharma A/S and Almirall. Dr Tu reports industry relationships with TOLMAR, Photocure, Graceway Pharmaceuticals, Apotex, Nycomed Pharma, and Teva Pharmaceutical Industries. Drs Knudsen, Erntoft, and Larsson are employees of LEO Pharma A/S. Dr Hanke reports industry relationships with Allergan, Dermik, Educational Testing and Assessment Systems, Eli Lilly, Elsevier, Galderma, Informa, Kythera, LEO Pharma A/S, Merz Pharma, Orlando Dermatology Aesthetic and Clinical, Sanova Dermatology, and Springer.

    Some of these data have been presented previously:

    • Berman B, Marmur E, Melgaard A. Three-day topical treatment with ingenol mebutate gel 0.015% for actinic keratoses on the face and scalp: analysis of data pooled from 2 trials. Poster P5623 presented at the Annual Meeting of the American Academy of Dermatology; San Diego, CA; March 16-20, 2012.

    • Anderson LL, Schmeider GJ, Xu Z, Melgaard A. Two-day topical treatment with ingenol mebutate gel 0.05% for actinic keratoses on the trunk and extremities: analysis of data pooled from 2 trials. Poster P5640 presented at the Annual Meeting of the American Academy of Dermatology; San Diego, CA; March 16-20, 2012.

    • Augustin M, Tu JH, Knudsen KM, Erntoft S, Larsson T, Hanke W. Effect of ingenol mebutate gel on treatment satisfaction and quality of life in actinic keratosis. E-poster P1645 (IST13-1530) presented at the 22nd Congress of the European Academy of Dermatology and Venereology; Istanbul, Turkey; October 3-6, 2013.

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