Topical resiquimod dosing regimens in patients with multiple actinic keratoses: a multicentre, partly placebo-controlled, double-blind clinical trial

Br J Dermatol. 2019 Feb;180(2):297-305. doi: 10.1111/bjd.17124. Epub 2018 Oct 22.

Abstract

Background: Topical immune response modifiers are established for actinic keratosis (AK) treatment and efforts are underway to make further improvements to their efficacy and safety.

Objectives: To investigate the optimal dosing regimens of the Toll-like receptor 7/8 agonist resiquimod in terms of efficacy, safety and tolerability.

Methods: In a multicentre, partly placebo-controlled, double-blind clinical trial, we randomized 217 patients with AK lesions to 0·03% resiquimod gel once-daily application three times per week for 4 weeks or seven times within 2 weeks or five times for 1 week (arms 1/2/3) followed by a treatment-free interval of 8 weeks and one repetition of the cycle. In two additional arms (arms 4/5), patients applied either resiquimod gel 0·01% or 0·03% three times per week up to a biological end point defined by skin erosion or for a maximum duration of 8 weeks. Clearance was assessed clinically and histologically.

Results: Complete clinical clearance ranged from 56% to 85% with the highest rate observed in arm 2. Resiquimod 0·03% gel was more effective than 0·01% gel. Clearance rates in arms 1/2/3 were comparable and higher than with placebo and were reached with 24, 14 and 10 gel applications, respectively. Overall, 128 patients (59%) experienced treatment-related adverse reactions.

Conclusions: Resiquimod 0·03% gel is more effective than 0·01% gel. From the perspectives of safety and tolerability, the lower concentration and shorter duration are preferable. The clinical response in arms 2/3 was reached with fewer gel applications. The dosing regimens that used the biological end point (arms 4/5) proved equally efficacious as predefined treatment durations and may therefore be suitable for personalized AK treatment.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / adverse effects
  • Aged
  • Aged, 80 and over
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Imidazoles / administration & dosage*
  • Imidazoles / adverse effects
  • Keratosis, Actinic / drug therapy*
  • Keratosis, Actinic / immunology
  • Male
  • Middle Aged
  • Placebos / administration & dosage
  • Placebos / adverse effects
  • Time Factors
  • Toll-Like Receptor 7 / agonists
  • Toll-Like Receptor 7 / immunology
  • Toll-Like Receptor 8 / agonists
  • Toll-Like Receptor 8 / immunology
  • Treatment Outcome

Substances

  • Adjuvants, Immunologic
  • Imidazoles
  • Placebos
  • TLR7 protein, human
  • TLR8 protein, human
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • resiquimod