E Stockfleth1, G F L Hofbauer2, U Reinhold3, G Popp4, U R Hengge5, R M Szeimies6, H Brüning7, M Anliker8, T Hunger9, R Dummer2, C Ulrich10, R Kenzelmann11, C Surber2,12, L E French2. 1. Universitätshautklinik, St. Josef-Hospital, Gudrunstrasse 56, 44791, Bochum, Germany. 2. Dermatologische Klinik, UniversitätsSpital Zürich, Gloriastrasse 31, 8091, Zürich, Switzerland. 3. Medizinisches Zentrum Bonn-Friedensplatz, Fachbereich Dermatologie, Allergologie, Dermatologische Onkologie, Friedensplatz 16, 53111, Bonn, Germany. 4. Licca Clinical Research Institute, Hofackerstrasse 19, 86179, Augsburg, Germany. 5. Hautzentrum Prof. Hengge, Immermannstrasse 10, 40210, Düsseldorf, Germany. 6. Klinikum Vest GmbH, Knappschaftskrankenhaus, Abteilung Dermatologie, Dorstener Strasse 151, 45657, Recklinghausen, Germany. 7. DERMAKIEL, Allergie und Hautzentrum, Schönberger Strasse 72-74, 24148, Kiel, Germany. 8. Dermatologie/Allergologie, Kantonsspital St. Gallen, Roschacher Strasse 95, 9007, St. Gallen, Switzerland. 9. Dermatologische Klinik, Inselspital, Universitätsspital Bern, Freiburgerstrasse 3, 3010, Bern, Switzerland. 10. Hauttumorzentrum Charité (HTCC), Klinik für Dermatologie, Venerologie und Allergologie, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. 11. Galderma Spirig Pharma AG, Froschackerstrasse 6, 4622, Egerkingen, Switzerland. 12. Dermatologische Klinik, Universitätsspital Basel, Petersgraben 4, 4031, Basel, Switzerland.
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.
RCT Entities:
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.
Authors: Judith C J Holzer-Geissler; Simon Schwingenschuh; Martin Zacharias; Johanna Einsiedler; Sonja Kainz; Peter Reisenegger; Christian Holecek; Elisabeth Hofmann; Barbara Wolff-Winiski; Hermann Fahrngruber; Thomas Birngruber; Lars-Peter Kamolz; Petra Kotzbeck Journal: Biomedicines Date: 2022-04-06