Trial Information

Actinic Keratoses and 5% Topical Imiquimod: Lessons to Learn From a Prospective Non-Interventional Study by 93 Office-based Dermatologists

DESIGN AND STUDY POPULATION The present study was a prospective, open label, non
interventional clinical study precisely documenting the routine therapy of AK with imiquimod
5% cream. According to Austrian regulations, for an observational study where medication
follows the label of the drug it is not necessary to seek approval from the federal ethic
committee. Except the presence of multiple AK there were no further rules to include the
patient into the study. Following the dermatologists decision and the patients will, 463
patients were treated in the offices of 93 non hospital based Austrian dermatologists. There
were no further interventions except recommended time points of visits documented with
pre-defined forms. Imiquimod therapy followed the label. Patients applied imiquimod at home
3x/week (typically Monday, Wednesday and Thursday) for 4 weeks, followed by 4 therapy free
weeks and another 3x/week 4 weeks therapeutic course, when needed. Recommended visits (V)
were: V1 baseline, week 0; V2, week 4 (end of the first treatment cycle); V3, week 8
(decision point for the need of a second treatment course); V4, week 16 (for those receiving
a second treatment course). Additional unplanned visits (VX) were possible and also
documented.

STUDY PROCEDURES At baseline patients characteristics, i.e. sex, age, size and weight were
documented together with the information who referred the patient to the dermatologist.
Next, the patient skin cancer family history and the AK history including the time of the
first presentation as well as former therapies and their success were asked. This was
followed by a dermatological examination which defined the numbers of AK lesions, their
location and the nature as well as intensity of initial skin signs (erosion, crusting,
erythema, ulceration, swelling, others, graded as no, mild, moderate, severe). Before the
start of the therapy, patients were informed about the typical imiquimod skin reactions by a
set of pictures and a brochure. In addition, all patients got a treatment plan showing the
different phases of the therapy and the time points when imiquimod should be applied. Within
this plan patients also had the possibility to document their imiquimod use. Also at
baseline, potential systemic and local co-medications were documented.

At all following visits, nature and intensity of Imiquimod related skin responses potential
adverse events and pre-final termination of the study were acknowledged. Decisions by the
dermatologists were documented as (i) nature of the topical post imiquimod treatment of
therapeutic skin reactions (V2, V3, V4, VX), (ii) initiation of a second therapeutic
course, or character of the alternative therapy (V3) as well as (iii) full clearing of all
lesions, or number of remaining lesions (V3, V4). At VX the dermatologist reaction to this
unplanned visit was asked (no consequences, temporary discontinuation of the therapy - how
long, topical treatment of the therapy related skin symptoms, or, pre-final termination of
the therapy). At the end of the study, reasons for a potential pre-final termination (lack
of efficacy, patients wish, adverse events, others), the kind of subsequent therapy for
remaining AK lesions, satisfaction of the dermatologist with the efficacy, tolerability and
the cosmetic outcome of the imiquimod therapy as well as patients general and specific
satisfaction with the cosmetic outcome and his estimation about the therapy success
including his grade of relief with the solved problem were delineated.