pep005 and methyl-5-aminolevulinate

The conclusions of pairwise meta-analyses of interventions for actinic keratosis (AK) are limited due to the lack of direct comparison between some interventions. Consequently, we performed a network meta-analysis for eight treatments [5-aminolaevulinic acid (ALA)-photodynamic therapy (PDT), cryotherapy, diclofenac 3% in 2·5% hyaluronic acid (DCF/HA), 5-fluorouracil (5-FU) 0·5% or 5·0%, imiquimod (IMI) 5%, ingenol mebutate (IMB) 0·015-0·05%, methyl aminolaevulinate (MAL)-PDT and placebo/vehicle (including placebo-PDT)] to determine their relative efficacies. As part of a prior Cochrane systematic review, different databases and grey literature were searched for randomized controlled trials up to April 2012. The inclusion criteria were parallel-group studies with nonimmunosuppressed participants: (i) reporting 'participant complete clearance' and (ii) comparing at least two of the interventions. Thirty-two publications met the criteria and they included the following number of individual or pooled studies (n) and total number of participants (N) for the different interventions: 5-FU 0·5% (n = 4, N = 169), 5-FU 5·0% (n = 2, N = 44), ALA-PDT (n = 6, N = 739), cryotherapy (n = 2, N = 174), DCF/HA (n = 5, N = 299), IMI (n = 14, N = 1411), IMB (n = 3, N = 560), MAL-PDT (n = 7, N = 557) and placebo (n = 32, N = 2520). Network analyses using a random-effects Bayesian model were carried out with the software ADDIS v1.16.1. The interventions were ranked as follows based on calculated probabilities and odd ratios: 5-FU > ALA-PDT ≈ IMI ≈ IMB ≈ MAL-PDT > cryotherapy > DCF/HA > placebo. This efficacy ranking was obtained based on the current available data on 'participant complete clearance' from randomized controlled trials and the analysis model used. However, several other factors should also be considered when prescribing a treatment for AK.

Topics: Adjuvants, Immunologic; Aged; Aminolevulinic Acid; Aminoquinolines; Anti-Inflammatory Agents, Non-Steroidal; Cryotherapy; Diclofenac; Diterpenes; Drug Combinations; Female; Fluorouracil; Follow-Up Studies; Humans; Hyaluronic Acid; Imiquimod; Immunocompetence; Immunosuppressive Agents; Keratosis, Actinic; Male; Middle Aged; Photochemotherapy; Photosensitizing Agents; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Aged; Aged, 80 and over; Aminolevulinic Acid; Diterpenes; Female; Fluorouracil; Humans; Imiquimod; Keratosis, Actinic; Male; Patient Reported Outcome Measures; Photochemotherapy; Quality of Life; Skin Cream; Surveys and Questionnaires; Treatment Outcome

Actinic keratosis (AK) is a common premalignant skin condition that might have the ability to progress into squamous cell carcinoma. Due to the high incidence of AK, treatment of this disease significantly impacts healthcare spending.. To determine which commonly prescribed field-directed treatment is the most cost-effective, when comparing 5-fluorouracil (5-FU) 5%, imiquimod (IMQ) 5%, ingenol mebutate (IM) 0·015% and methyl aminolaevulinate photodynamic therapy (MAL-PDT) for AK in the head and neck region.. We performed an economic evaluation from a healthcare perspective. Data were collected alongside a single-blinded, prospective, multicentre randomized controlled trial with 624 participants in the Netherlands. The outcome measure was expressed as the incremental cost-effectiveness ratio, which is the incremental costs per additional patient with ≥ 75% lesion reduction compared with baseline. This trial was registered at ClinicalTrials.gov, number NCT02281682.. The trial showed that 5-FU was the most effective field treatment for AK in the head and neck region. Twelve months post-treatment, the total mean costs for 5-FU were significantly lower (€433) than the €728, €775 and €1621 for IMQ, IM and MAL-PDT, respectively. The results showed that 5-FU was a dominant cost-effective treatment (more effective and less expensive) compared with the other treatments, 12 months post-treatment.. Based on these results, we consider 5-FU 5% cream as the first-choice treatment option for multiple AKs in the head and neck area. What's already known about this topic? Due to the increasing incidence of actinic keratosis (AK), the recommended treatment results in a considerable socioeconomic burden for (dermatological) healthcare. Although cost-effectiveness modelling studies have been performed in which different treatments for AK were compared, a prospective clinical trial comparing four frequently prescribed treatments on effectiveness and resource consumption within a time horizon of 12 months has never been conducted. What does this study add? This is the first study examining the cost-effectiveness of 5-fluorouracil 5% cream, imiquimod 5% cream, ingenol mebutate 0·015% gel and methyl aminolaevulinate photodynamic therapy, with data collected in a randomized controlled trial over a time horizon of 12 months. We found that 5-fluorouracil was a dominant cost-effective treatment (more effective and less costly), based on data from the Netherlands. Linked Comment: Steeb et al. Br J Dermatol 2020; 183:612.

Topics: Aminolevulinic Acid; Cost-Benefit Analysis; Diterpenes; Fluorouracil; Humans; Imiquimod; Keratosis, Actinic; Netherlands; Photochemotherapy; Photosensitizing Agents; Prospective Studies; Treatment Outcome

Actinic keratosis is the most frequent premalignant skin disease in the white population. In current guidelines, no clear recommendations are made about which treatment is preferred.. We investigated the effectiveness of four frequently used field-directed treatments (for multiple lesions in a continuous area). Patients with a clinical diagnosis of five or more actinic keratosis lesions on the head, involving one continuous area of 25 to 100 cm. A total of 624 patients were included from November 2014 through March 2017. At 12 months after the end of treatment, the cumulative probability of remaining free from treatment failure was significantly higher among patients who received fluorouracil (74.7%; 95% confidence interval [CI], 66.8 to 81.0) than among those who received imiquimod (53.9%; 95% CI, 45.4 to 61.6), MAL-PDT (37.7%; 95% CI, 30.0 to 45.3), or ingenol mebutate (28.9%; 95% CI, 21.8 to 36.3). As compared with fluorouracil, the hazard ratio for treatment failure was 2.03 (95% CI, 1.36 to 3.04) with imiquimod, 2.73 (95% CI, 1.87 to 3.99) with MAL-PDT, and 3.33 (95% CI, 2.29 to 4.85) with ingenol mebutate (P≤0.001 for all comparisons). No unexpected toxic effects were documented.. At 12 months after the end of treatment in patients with multiple actinic keratosis lesions on the head, 5% fluorouracil cream was the most effective of four field-directed treatments. (Funded by the Netherlands Organization for Health Research and Development; ClinicalTrials.gov number, NCT02281682.).

Topics: Aged; Aged, 80 and over; Aminolevulinic Acid; Diterpenes; Female; Fluorouracil; Follow-Up Studies; Gels; Humans; Imiquimod; Intention to Treat Analysis; Keratosis, Actinic; Male; Middle Aged; Patient Compliance; Photochemotherapy; Photosensitizing Agents; Proportional Hazards Models; Scalp Dermatoses; Single-Blind Method; Skin Cream; Treatment Outcome

Daylight-photodynamic therapy (D-PDT) and ingenol mebutate (IM) are novel therapies directed to actinic keratoses (AK). The purpose of our study was to compare effectiveness, tolerability, cosmetic outcome and patient preference of D-PDT versus IM in the treatment of grade I and II AK. Twenty-seven patients with AK on the face or scalp were enrolled. Each patient received, in a 25 cm(2) target area, D-PDT on right side and IM on left side. Overall 323 AK were treated. Both target areas achieved complete response in 40.47% of the cases and average AK clearance rate was similar for D-PDT and IM (p=0.74). In D-PDT areas mean grade II AK clearance rate was lower compared with that of grade I AK (p=0.015). In IM areas grade I and II AK average clearance rates were similar (p=0.28). At week 1 and month 1, mean local skin responses (LSR) score were higher in areas treated with IM. IM areas showed more severe pain and cosmetic sequelae. D-PDT had similar effectiveness to IM, even if IM demonstrated higher grade II AK clearance rate. Tolerability profile was superior for D-PDT in terms of LSR and pain. D-PDT was more cosmetically acceptable. Patients preferred D-PDT to IM in most cases.

Topics: Aged; Aged, 80 and over; Aminolevulinic Acid; Dermatologic Agents; Diterpenes; Facial Dermatoses; Female; Humans; Keratosis, Actinic; Male; Middle Aged; Patient Preference; Photochemotherapy; Photosensitizing Agents; Remission Induction; Scalp Dermatoses; Sunlight; Surveys and Questionnaires; Time Factors; Treatment Outcome

Daylight photodynamic therapy with methyl aminolaevulinate (dlPDT) and ingenol mebutate gel (IMB) are approved therapeutic options for multiple actinic keratoses (AKs). The aim of this comparative, intra-patient, split-face, randomized clinical trial was to compare treatment outcomes of dlPDT and IMB.. Two symmetrical contralateral areas of 25cm. 22 patients with a total of 311 AKs were enrolled. The mean pain VAS score was 3.55±1.82 with IMB and 2.05±0.72 with dlPDT (p<0.01). The mean LSR score was 9.91±4.24 and 4.59±4.03 (p<0.01), respectively. The mean days necessary for wound closure were 9.45±3.51 and 4.36±1.18days (p<0.01), respectively. After 3 months, 119 lesions with IMB and 120 lesions with dlPDT were healed and the CR rate with IMB (75.8%) was non-inferior to the CR rate with dlPDT (77.9%). The comparisons of CR rates of grade I and II AKs did not show any inferiority for one treatment compared to the other. Eight patients (36.4%) had all lesions cleared with IMB and 7 (31.8%) with dlPDT (p=NS). The cosmetic outcome was better with dlPDT and 17 patients evaluated dlPDT as their preferred treatment.. A 3days' treatment cycle with IMB and a single session of dlPDT had a similar efficacy for both grade I AKs and grade II AKs but dl PDT showed lower pain and inflammation scores, quicker wound closure, better cosmetic outcome and higher patients' preference.

Topics: Aged; Aged, 80 and over; Aminolevulinic Acid; Diterpenes; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Drug Administration Schedule; Facial Dermatoses; Female; Gels; Humans; Keratosis, Actinic; Male; Middle Aged; Patient Preference; Photochemotherapy; Scalp Dermatoses; Treatment Outcome

Photodynamic therapy with methyl aminolevulinate (MAL-PDT) and ingenol mebutate gel (IMB) are approved therapeutic options for multiple actinic keratoses (AKs).. The aim of this intraindividual, split-face, randomized clinical trial was to compare treatment outcomes of MAL-PDT and IMB.. Two symmetrical contralateral areas with a similar number of AKs were selected and randomly assigned to 3 days of an IMB treatment cycle or a single session of MAL-PDT. The next day, the local skin reaction (LSR) score was registered. The patients scored pain and time to healing of the treatment area.. After 90 days, the complete remission rate of lesions, the number of patients with complete remission of all lesions, cosmetic outcome, and patient preference were assessed.. According to our results, IMB and MAL-PDT had a similar efficacy, but the cosmetic outcome was superior with MAL-PDT. Pain was higher with PDT, but LSR was more severe and time to healing was longer with IMB. Patients preferred MAL-PDT.

Topics: Administration, Topical; Aged; Aged, 80 and over; Aminolevulinic Acid; Diterpenes; Face; Facial Dermatoses; Female; Follow-Up Studies; Gels; Humans; Keratosis, Actinic; Male; Middle Aged; Photochemotherapy; Photosensitizing Agents; Remission Induction; Retrospective Studies; Scalp; Scalp Dermatoses; Skin; Treatment Outcome

Actinic keratoses (AKs) are common skin lesions association with increased exposure to ultraviolet radiation; these lesions have the potential to transform into squamous cell carcinomas (SCCs).1.

Topics: Aminolevulinic Acid; Carcinoma, Squamous Cell; Clinical Trials as Topic; Diterpenes; Fluorouracil; Humans; Imiquimod; Incidence; Keratosis, Actinic; Patient Preference; Photochemotherapy; Photosensitizing Agents; Risk Assessment; Skin Neoplasms; Treatment Outcome

Topics: Aminolevulinic Acid; Cost-Benefit Analysis; Diterpenes; Fluorouracil; Humans; Imiquimod; Keratosis, Actinic; Netherlands; Photochemotherapy

Topics: Adult; Aminolevulinic Acid; Diterpenes; Fluorouracil; Humans; Imiquimod; Keratosis, Actinic; Photochemotherapy; Scalp Dermatoses

The cost of topical treatments for actinic keratosis (AK) has historically been evaluated in relation to the number of lesions requiring treatment or simply by the price of a single tube/sachet of the drug used.. To demonstrate a new method of costing topical treatments in AK, which takes into account the actual cancerization area treated.. In order to evaluate the actual cost of each treatment, the official approval status of the drug was used to estimate the amount of cream needed per one cm. Areas which could be treated with a single tube/sachet of Metvix. Changing treatment costing strategy in the management of multiple AKs towards costing per cancerization area instead of costing per lesion is a much more accurate representation of the 'real world cost' for AK.

Topics: Administration, Topical; Aminolevulinic Acid; Cohort Studies; Cost of Illness; Diclofenac; Diterpenes; Drug Administration Schedule; Female; Fluorouracil; Health Care Costs; Humans; Imiquimod; Italy; Keratosis, Actinic; Male; Photochemotherapy; Precancerous Conditions; Retrospective Studies; Risk Assessment; Severity of Illness Index; Treatment Outcome

Field-directed therapy, such as daylight-photodynamic therapy (DL-PDT) or ingenol mebutate (IM), is indicated for multiple actinic keratosis (AK) lesions located on contiguous areas of skin with significant sun damage.. To compare the efficacy of sequential DL-PDT and IM treatment with that of 2 sessions of DL-PDT in AK patients.. For this observational, multicenter, prospective study we recruited patients for whom DL-PDT was indicated for the treatment of AK lesions (grades I and II) located on the head. After 1 month of follow-up those who did not achieve a satisfactory clinical response received either a second session of DL-PDT or were treated with IM. Epidemiological and clinical data were collected and analyzed.. Forty-three patients were enrolled (39 male, 4 female). The mean (standard deviation, SD) age was 78 (7.84) years, and the mean (SD) number of AK lesions per patient was 9.58 (1.16). After the first session of DL-PDT, 27 patients (62.8%) required further treatment: 13 (48.1%) received a second session of DL-PDT and 14 (51.9%) were treated with IM. After 1 year of follow-up, lesion clearance rates were higher in patients who received 2 sessions of DL-PDT than those treated with sequential DL-PDT plus IM (75.2%vs 54.6%, p = 0.0013). Local skin reactions were more frequent in the DL-PDT plus IM group than the group treated with 2 sessions of DL-PDT (p = 0.0245).. The combination of DL-PDT plus IM appears to have no synergistic effect in the treatment of field cancerization, and offers no benefits over 2 sessions of DL-PDT monotherapy, although both combinations produced high lesion clearance rates, a good safety profile, excellent cosmetic outcome, and good patient satisfaction.

Topics: Aged; Aged, 80 and over; Aminolevulinic Acid; Diterpenes; Drug Therapy, Combination; Female; Humans; Keratosis, Actinic; Male; Patient Satisfaction; Photochemotherapy; Photosensitizing Agents; Pilot Projects; Prospective Studies; Sunlight

We present the case of a 73-year-old male patient who had received a first renal transplant at 36 years and a second one at the age of 55 years. He is currently under immunosuppression with everolimus 2.5 mg/day and prednisone 5 mg/day. The patient presented with multiple actinic keratoses on both cheeks and the forehead and received treatment by ingenol mebutate 150 µg/g gel daily on 3 consecutive days on his right cheek and methyl aminolevulinate (MAL) photodynamic therapy activated by daylight (MAL-dPDT) on the forehead and the left cheek. MAL-dPDT treatment proved a feasible, repeatable, physician-directed method of treating field cancerization with limited morbidity for a period of 6 days. Treatment with ingenol mebutate gel was a feasible, possibly self-directed method of treating field cancerization with limited morbidity for 10 days in this immunosuppressed patient. Both treatments showed similar efficacy. At the time of treatment, the MAL daylight PDT ran at 3 times the cost of ingenol mebutate gel.

Topics: Aged; Aminolevulinic Acid; Antineoplastic Agents; Carcinogenesis; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Diterpenes; Face; Humans; Keratosis, Actinic; Kidney Transplantation; Male; Photochemotherapy; Photosensitizing Agents; Skin Neoplasms; Transplant Recipients