TABLE 3a.
| First author | Study design | AK location | Treatment administered | Adherence to treatment | PROs | |
|---|---|---|---|---|---|---|
| Instrument utilized | Main findings | |||||
| Augustin et al. | Post‐hoc analyses from four phase‐III, multi‐center, randomized, double‐blind, vehicle‐controlled trials | Face, scalp, trunk and extremities | 0.015% ingenol mebutate for 3 days or 0.05% for 2 days | From 98.2% to 98.7% | TSQM, Skindex‐16 | Significant, positive associations between TSQM score and degree of clearance were identified for patients in Significant association between Skindex‐16 score and clearance for patients in the face/scalp group for change in symptoms. Emotions, and overall Skindex‐16 score from baseline. |
| Berman et al. | Phase II, multicenter, open‐label trial | Any part of the body (face, chest, scalp, trunk or extremities), with no lesions (from 74.2% to 85.7%), 1‐2 lesions (from 11.1% to 11.3%), | Ingenol disoxate gel applied once daily for 3 consecutive days (0.018% for face and chest, 0.037% for scalp and 0.1% for trunk or extremities) | 97% (from 95% to 98%, depending on the specific area) | TSQM, cosmetic outcome questionnaire | Treatment satisfaction score ranging from 66.7/100 to 91.3/100. Based on the specific area, global satisfaction scores were 73.9/100, 79.7/100, 66.7/100 for the face/chest, scalp, and trunk/extremities groups, respectively |
| Emilio et al. | Prospective pilot study | Face | 0.015% ingenol mebutate gel applied once daily for 3 consecutive days | NR | Skindex‐16 | Mean overall scores improved from 24.5% at baseline to 15.5% as assessed on day 60. More in detail, treatment impacted on quality of life in a large and positive way for patients with mild and moderate LSR (Cohen's 2.1 and 1.8, respectively) and had, instead, little impact in patients with severe LSR (Cohen's d 0.2) |
| Gameiro et al. | Retrospective, descriptive, observational | Face and scalp | 0.015% ingenol mebutate gel for 3 days | 100% | Ad hoc non validated questionnaire | Perception of the treatment: great (75.68%) |
| Discomfort: reasonable (40.54%), no discomfort (13.1%) | ||||||
| Adverse reactions: erythema and local pruritus (16%) particularly disturbing | ||||||
| Self‐esteem: improved in 97.30% cases | ||||||
| Overall score: 9.4 (7–10) | ||||||
| Hanke et al. | Phase 3, randomized, parallel‐group, double‐blind, vehicle‐controlled trial | Face, scalp, chest | Ingenol mebutate 0.027% gel | 4 patients drop‐out | TSQM and Skindex‐16 | Patients who recieved ingenol mebutate were more satisfied. |
| Jubert‐Esteve et al. | Prospective, non randomized pilot study | Any part of the body | Imiquimod 5% and ingenol mebutate | 0 drop out | TSQM and Skindex‐29 | After treatment with ingenol mebutate, significant improvement was observed in the Skindex‐29 subscales relating to symptom severity, the patients' emotional state, and in the overall score. Imiquimod 5% and ingenol mebutate achieved higher median scores for effectiveness and global satisfaction than any other previous treatments (as measured by TSQM 1.4) |
| Neri et al. | Observational, multicentre, longitudinal, cohort study | Any part of the body | Ingenol mebutate, diclofenac, hyaluronic acid, Imiquimod 5% | 46% avoided application within 2 h before bedtime, 14% washed the treated area erlier than 6 h post application. Patients undergoing long term treatment skip more than 20% of the applications in 5.2% of ingenol treated patients and in 74% of patients treated with different topical drugs | TSQM, PHQ4, ad hoc questionnaire‐based measures | Treatment satisfaction was higher for ingenol mebutate. Clarity in the communication between the physician and the patient was associated with a higher adherence and treatment satisfaction |
| Norrlid et al. | Observational, multicentre, real‐life study | Any part of the body, with 9.4 ± 8.2 lesions on average | diclofenac gel, imiquimod 3.75% or 5% or ingenol mebutate 150 μg/g or 500 μg/g | Treatment adherence was generally high, but higher for ingenol mebutate compared to both diclofenac (p < .001) and imiquimod (p = .007), possibly due to shorter treatment duration | TSQM‐9, MMAS, EQ‐5D‐5L, EQ‐VAS, AKQoL | Treatment satisfaction was higher for ingenol mebutate compared to patients treated with diclofenac |
| Platsidaki et al. | Noninterventional multicenter study | Face (61.6%), Scalp (32.5%) and others (5.9%) | Face and scalp: 150 mcg/g ingenol mebutate gel during 3 consecutive days; Other locations: 500 mcg/g ingenol mebutate gel for 2 days | 100% | EQ‐5D questionnaire, EQ VAS and TSQM‐9 | Patients reported high satisfaction, especially in case of complete AK clearance. |
| Schlaak et al. | Single center, prospective study | Face/Head | Solution of 5 mg fluorouracil (0.5%) and 100 mg salicylic acid (10%) 3 times per day for 4 weeks | 1 patient drop‐out due to side effects | Treatment satisfaction VAS | Patients satifaction was “good” |
| Segatto et al. | Randomized, parallel‐group clinical trial | Face, Scalp and Back of the hands | 3% diclofenac sodium with 2.5% hyaluronic acid gel twice daily for 12 weeks vs. 5% 5‐Fluorouracil cream twice daily for 4 weeks | 3 patients drop‐out in the 5FU group. | Treatment satisfaction VAS | In relation to satisfaction regarding the adverse effects, the group treated with DFS showed higher satisfaction compared to the group treated with 5‐FU, with 93.3% and 38.4% of highly satisfied patients, respectively. Regarding the patients' evaluation, most were highly satisfied with the improvement of the lesions in both groups, with no statistically significant difference. When considering the degree of improvement, more than half of the patients (54%) in the group treated with 5‐FU considered themselves to be fully healed, compared to 20% in the group treated with DFS. |
| Stockfleth et al. | Phase III, multicenter, randomized, double‐blind, vehicle‐controlled study | Scalp and face/forehead | 5‐FU 0.5% plus salicylic acid 10% | 2 patients drop‐out | TSQM and DLQI | Treatment satisfaction scores were higher in treated patients when compared to vehicle. No statistically significant differences were observed between the study arms for the TSQM convenience and side effect domain scores. |
| Strydom et al. | Single‐center, prospective, questionnaire‐based study | Face | 0.015% ingenol mebutate applied once daily for 3 consecutive days, over areas up to 100 cm2 | NR | Ad hoc, nonvalidated 11‐item questionnaire | Treatment satisfaction was rather high (86‐89%). Pretreatment education was appreciated by all patients. |
| 58% patients experienced moderate‐to‐severe pain. 51%, 41% and 9% found their appearance, pain and anxiety particularly distressing, respectively. 31% would have discontinued the treatment in case of self‐application, with 82% preferring in‐clinic application | ||||||
| Waalboer‐Spuij et al. | Multicenter open‐label study | Any part of the body, with 1 lesion (25%), 2–4 lesions (13%), 5‐9 lesions (29%), ≥10 lesions (31%) | 5% imiquimod cream once daily, 3 days per week, for 4 weeks | 6‐7% of patients decided to discontinue the therapy | Skindex‐17, TSQM, SCI adapted to AK | Imiquimod had no impact on health‐related quality of life. Overall treatment satisfaction was less than 60/100 |
Abbreviation: NR ‐ Not reported.