Safety and efficacy of the combination of cryotherapy and photodynamic modalities with imiquimod in patients with actinic keratosis: a systematic review and meta-analysis

INTRODUCTION: Actinic keratosis (AK) is an intraepithelial tumor that, in most cases, arises in chronically sun-exposed areas. The combination of cryotherapy and photodynamic modalities with imiquimod has been proven to be a potential therapeutic option for AKs. However, there is no comprehensive systematic study that discussed this concept in literature taking into consideration both efficacy and safety. EVIDENCE ACQUISITION: We performed a comprehensive search of the literature for studies assessing the efficacy and toxicity of the combinatorial tripartite regimen, consisting of cryotherapy and photodynamic modalities with imiquimod in AK. Metanalysis was performed using comprehensive meta-analysis version 3.0. EVIDENCE SYNTHESIS: After the screening of 1031 studies, five studies were included. Two trials compared the effect of imiquimod/cryotherapy versus cryotherapy alone or versus cryotherapy/vehicle. Our meta-analysis indicated that imiquimod/cryotherapy effectively induces complete clinical clearance in patients with AKs (OR: 6.26; 95%CI: 1.56-24.1; P=0.01). Moreover, another two studies, which were not meta-analyzed, indicated a substantial clinical clearance in the number of AK lesions in the imiquimod plus photodynamic therapy arm as compared to 5% imiquimod or PDT alone. No serious systemic adverse events were reported in all the treatment arms. CONCLUSIONS: Combined PDT or cryotherapy with imiquimod is more effective in the complete recovery of AK than treatment with imiquimod alone.