Topical resiquimod dosing regimens in patients with multiple actinic keratoses: a multicentre, partly placebo‐controlled, double‐blind clinical trial. (1st February 2019)

• Record Type: Journal Article
• Authors: Stockfleth, E.; Hofbauer, G.F.L.; Reinhold, U.; Popp, G.; Hengge, U.R.; Szeimies, R.M.; Brüning, H.; Anliker, M.; Hunger, T.; Dummer, R.; Ulrich, C.; Kenzelmann, R.; Surber, C.; French, L.E.
• Is Part Of: British journal of dermatology. Volume 180:Number 2(2019)
• Page Start: 297
• Page End: 305
• Publication Date: 2019-02-01
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.17124
• Languages: English
• ISSNs: 0007-0963

Abstract

Summary: 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.