A randomized, intraindividual, non-inferiority, Phase III study comparing daylight photodynamic therapy with BF-200 ALA gel and MAL cream for the treatment of actinic keratosis

J Eur Acad Dermatol Venereol. 2019 Feb;33(2):288-297. doi: 10.1111/jdv.15185. Epub 2018 Aug 14.

Abstract

Background: The most effective treatment modality for actinic keratosis (AK) is photodynamic therapy (PDT). Major obstacles of PDT are the need of a special illumination device and pain accompanying the illumination. These issues may be overcome by replacing an artificial high-power light source with natural daylight for more extended illumination at lower light doses.

Objective: To determine whether BF-200 ALA (a nanoemulsion gel containing 7.8% 5-aminolaevulinic acid) is non-inferior to MAL (a cream containing 16% methyl-aminolaevulinate) in the treatment of mild-to-moderate AK with daylight PDT (dPDT). Non-inferiority of the primary efficacy variable (total lesion clearance rate per patient's side 12 weeks after PDT) is established if the mean response for BF-200 ALA is no worse than for MAL, within a statistical margin of Δ = -12.5%.

Methods: The study was performed as an intraindividual comparison with 52 patients in seven centres in Germany and Spain. Each patient received one dPDT. Results include clinical endpoints as well as 1-year follow-up results.

Results: Twelve weeks after a single dPDT, 79.8% of the AK lesions treated with BF-200 ALA gel and 76.5% of the lesions treated with MAL cream were completely cleared. The median of differences was 0.0 with a one-sided 97.5% CI of 0.0, establishing non-inferiority (P < 0.0001). Results for secondary efficacy parameters were in line with the primary outcome. Recurrence rates 1 year after the treatment were 19.9% for lesions treated with BF-200 ALA and 31.6% for lesions treated with MAL. Adverse reactions including pain were mostly mild and transient and identical to those previously described for dPDT.

Conclusion: Daylight PDT of AK with BF-200 ALA is well-tolerated and non-inferior to MAL/dPDT. The study demonstrates a trend towards higher efficacies after 3 months and significantly lower recurrence rates after 1 year follow-up.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Cutaneous
  • Aged
  • Aminolevulinic Acid / administration & dosage
  • Aminolevulinic Acid / analogs & derivatives*
  • Female
  • Gels / therapeutic use
  • Germany
  • Humans
  • Keratosis, Actinic / diagnosis*
  • Keratosis, Actinic / drug therapy*
  • Male
  • Photochemotherapy / methods*
  • Photosensitizing Agents / administration & dosage*
  • Prognosis
  • Severity of Illness Index
  • Skin Cream / therapeutic use
  • Spain
  • Statistics, Nonparametric
  • Treatment Outcome

Substances

  • BF-200 ALA
  • Gels
  • Photosensitizing Agents
  • methyl 5-aminolevulinate
  • Aminolevulinic Acid