PMID- 27518593
OWN - NLM
STAT- MEDLINE
DCOM- 20171003
LR  - 20171003
IS  - 1365-2133 (Electronic)
IS  - 0007-0963 (Linking)
VI  - 176
IP  - 1
DP  - 2017 Jan
TI  - Histological examination confirms clinical clearance of actinic keratoses 
      following treatment with ingenol mebutate 0.05% gel.
PG  - 71-80
LID - 10.1111/bjd.14968 [doi]
AB  - BACKGROUND: To date, studies with ingenol mebutate gel have used clinical 
      clearance, not histological clearance, as a primary efficacy endpoint. 
      OBJECTIVES: This phase I, multicentre, single-arm, open-label study sought to 
      confirm histologically the clinical clearance of actinic keratoses (AKs) to 
      support a treatment effect deep in the epidermis. METHODS: Patients (n = 108) 
      aged >/= 18 years with histologically confirmed AK within a 25-cm(2) contiguous 
      treatment area on the trunk and extremities received ingenol mebutate 0.05% gel 
      for two consecutive days and were followed up on day 3 and week 8. One AK was 
      randomly preselected at day 1 for clinical and histological evaluation at week 8 
      and for reflectance confocal microscopy (RCM) in a subset of patients. The 
      primary endpoint was clinical and histological clearance of AKs at week 8. 
      RESULTS: The observed agreement rate between clinical and histological 
      assessments of clearance of a single AK was 81.9% and the positive predictive 
      value of a clinical assessment of clearance was 87%. Agreement between the two 
      pathologists was 88%. The common composite 8-week complete clearance rate was 41% 
      (95% confidence interval 32-50). Observed agreement rates between RCM and 
      pathologist I and II assessments of clearance were 72.9% and 81.4%, respectively. 
      Overall, 30 patients (27.8%) experienced 38 adverse events (AEs). 
      Application-site pain (four patients, 3.7%) was the most common treatment-related 
      AE inside the treatment area. CONCLUSIONS: Ingenol mebutate achieves 
      histopathological clearance of AKs that correlates with observed clinical 
      clearance. Clinical clearance is a good predictor for histological clearance.
CI  - (c) 2016 British Association of Dermatologists.
FAU - Ulrich, M
AU  - Ulrich M
AD  - Charite Universitatsmedizin Berlin, Department of Dermatology, Chariteplatz 1, 
      Berlin, Germany.
AD  - Dermatologie am Regierungsviertel/Collegium Medicum, Berlin, Germany.
FAU - Reinhold, U
AU  - Reinhold U
AD  - Department of Dermatology, Dermatological Center Bonn Friedensplatz, 
      Friedensplatz, Bonn, Germany.
FAU - Skov, T
AU  - Skov T
AD  - LEO Pharma A/S, Ballerup, Denmark.
FAU - Elvang Sondergaard, R
AU  - Elvang Sondergaard R
AD  - LEO Pharma A/S, Ballerup, Denmark.
FAU - Guitera, P
AU  - Guitera P
AD  - Sydney Melanoma Diagnostic Centre and Melanoma Institute Australia, Discipline of 
      Dermatology, The University of Sydney, Sydney, NSW, Australia.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
DEP - 20161207
PL  - England
TA  - Br J Dermatol
JT  - The British journal of dermatology
JID - 0004041
RN  - 0 (3-ingenyl angelate)
RN  - 0 (Dermatologic Agents)
RN  - 0 (Diterpenes)
RN  - 0 (Gels)
SB  - IM
MH  - Administration, Cutaneous
MH  - Aged
MH  - Dermatologic Agents/*administration & dosage
MH  - Diterpenes/*administration & dosage
MH  - Female
MH  - Gels
MH  - Humans
MH  - Keratosis, Actinic/*drug therapy/pathology
MH  - Male
MH  - Microscopy, Confocal
MH  - Observer Variation
MH  - Treatment Outcome
EDAT- 2016/08/16 06:00
MHDA- 2017/10/04 06:00
CRDT- 2016/08/13 06:00
PHST- 2016/06/15 00:00 [accepted]
PHST- 2016/08/16 06:00 [pubmed]
PHST- 2017/10/04 06:00 [medline]
PHST- 2016/08/13 06:00 [entrez]
AID - 10.1111/bjd.14968 [doi]
PST - ppublish
SO  - Br J Dermatol. 2017 Jan;176(1):71-80. doi: 10.1111/bjd.14968. Epub 2016 Dec 7.