Topical simvastatin–cholesterol for disseminated superficial actinic porokeratosis: An open‐label, split‐body clinical trial

Abstract

Background/Objectives: Disseminated superficial actinic porokeratosis (DSAP) is a porokeratosis variant that is cosmetically disfiguring and may be associated with squamous cell carcinoma. It is an autosomal dominant condition caused by germline mutations in mevalonate pathway genes involved in cholesterol synthesis. Lesions are precipitated by ultraviolet radiation-induced second-hit mutations. Modulation of this pathway by topical simvastatin-cholesterol may lead to improvement.Methods: This open-label, split-body clinical trial was carried out in 2020 at a metropolitan dermatology clinic. Eight patients contributing 13 limb pairs were recruited. Limbs within each pair were randomly allocated to 2% simvastatin/2% cholesterol cream applied twice daily or bland emollients. Lesion number, erythema, scale and patientreported disease activity were measured at baseline and 6 weeks. Data were analysed using Bayesian ordinal logistic regression. Odds ratios compare the odds of a higher score at 6 weeks in treated limbs with the odds in controls. Values less than one indicate improvement.Results: Patients had a median age of 65 years (interquartile range [IQR] 58 to 69 years). The median baseline DLQI was 5 (range 2-21). Odds ratios were 0.12 (95% credible interval [CI] 0.01 to 0.72) for lesion number, 0.25 (95% CI 0.05 to 0.79) for erythema score, 0.18 (95% CI 0.03 to 0.64) for scale score and 0.33 (95% CI 0.09 to 0.89) for patientreported disease activity. Conclusions:Topical simvastatin-cholesterol cream improved lesion number, erythema and scale on treated limbs compared with controls. Patientreported disease activity also improved. These findings warrant confirmation in blinded, vehiclecontrolled trials.

Simvastatin cream alleviates dermal fibrosis in a rabbit ear hypertrophic scar model

“…Since xerosis is an undesirable side effect of topical statin treatment, we wished to determine whether withdrawal of statin-containing cream treatment would lead to resolution of dryness. Excisional wounds and treatment with 10% simvastatin cream were performed again as described in Figure 1 absent reported adverse events in human patients [16][17][18][19] and in animal models, 6,7,20,21 suggesting that local application of statin drugs is generally safe. In addition to the active component, safety of the delivery vehicle is also critical to minimize adverse effects resulting from topical application.…”

“…One advantage to topical delivery for local administration is restriction of the delivery of a drug, and hence its activity, to a defined location, minimizing concerns of toxicity systemically or in organs distant from the target of interest. Topical administration of statins for dermatologic indications has previously been utilized absent reported adverse events in human patients 16 , 17 , 18 , 19 and in animal models, 6 , 7 , 20 , 21 suggesting that local application of statin drugs is generally safe. In addition to the active component, safety of the delivery vehicle is also critical to minimize adverse effects resulting from topical application.…”

Safety and Efficacy of Topical Lovastatin Plus Cholesterol Cream vs Topical Lovastatin Cream Alone for the Treatment of Disseminated Superficial Actinic Porokeratosis

“…Other statin derivatives have also shown success. An open-labeled, unblinded, split-body study compared simvastatin 2% plus cholesterol 2% with bland emollients in 8 participants for 6 weeks. The treated limbs had improvements in lesion number, erythema, and scale compared with the limbs receiving emollients.…”