Phase 1 Randomized Trial Supports Lovastatin as a Potential Primary Treatment for Disseminated Superficial Actinic Porokeratosis

1. Disseminated superficial actinic porokeratosis (DSAP) was improved in both treatment groups (i.e., lovastatin-cholesterol and lovastatin alone) with no serious adverse events.

2. Lovastatin cream alone could be a new primary treatment option for DSAP.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Disseminated superficial actinic porokeratosis (DSAP) is an inherited or sporadic disorder, most commonly seen in White women in their 30s or 40s, characterized by multiple, sun-exposed, pink or brown erythematous plaques or macules. Although DSAP is often benign, malignancy is possible. As there is no effective standard of care treatments for DSAP, this randomized control trial evaluated the safety profile and efficacy of topical lovastatin 2% plus cholesterol 2% cream (lovastatin-cholesterol) and topic lovastatin 2% cream alone in adults with DSAP. Lovastatin inhibits β-hydroxy-β-methylglutaryl-CoA (HMG-CoA) reductase, blocking toxic metabolite accumulation and inhibiting hyperactive immune responses. Additionally, lovastatin also blocks the production of cholesterol. Of the 31 participants, DSAP severity decreased more in the lovastatin-alone group when compared to the lovastatin-cholesterol group. Application frequency was not significantly different between the two treatment groups, and no serious adverse events occurred. Some limitations include lack of funding, virtual appointments (due to COVID-19), the small sample size, short follow-up timelines, the lack of a placebo group, and participant-taken photographs. Histopathological confirmation of diagnoses was not conducted in 21 participants, and genetic confirmation was not completed for any participant. Furthermore, a nonvalidated assessment scale adapted from a validated psoriasis assessment scale was used due to the lack of DSAP literature.

Click to read the study in JAMA Dermatology

Relevant Reading: Topical cholesterol/lovastatin for the treatment of porokeratosis: A pathogenesis-directed therapy

In-Depth [randomized control trial]: This phase 1, randomized, double-blinded, single-center study, spanning August 3, 2020, to April 28, 2021, at the Medical University of South Carolina, investigated the safety profile and efficacy of topical lovastatin 2% plus cholesterol 2% cream (lovastatin-cholesterol) and topic lovastatin 2% cream alone in adults with DSAP. The primary objective of this trial was to compare the effectiveness of the two treatment groups [Disseminated Superficial Actinic Porokeratosis General Assessment Severity Index (DSAP-GASI)], whereas the secondary objectives were participant-reported outcomes, the frequency of application, and adverse events. The RAND-36 Measure of Health-Related Quality of Life and the Dermatology Life Quality Index were used to investigate participants’ quality of life. Participant inclusion criteria included being 18 years or older, residing in South Carolina, North Carolina, or Pennsylvania and having a clinical or histological diagnosis of DSAP. Participants who used study drugs within 4 weeks of the beginning of the study, had allergies or contraindications to lovastatin or cholesterol, were outside of the inclusion jurisdiction, were pregnant, were breastfeeding, or were planning to become pregnant within the study period were excluded. The initial funding was decreased during the COVID-19 pandemic, and the participants had to pay wholesale discounted drug costs. 87 participants were screened, 32 were allocated to treatment groups using computer-generated block randomization, and 31 were followed for 12 weeks. The lovastatin-cholesterol group consisted of 17 participants (mean [range] age, 59.2 [40-83] years; 13 females [76.5%]; all White). The lovastatin alone group consisted of 14 participants (13 female [92.9%]; mean (range) age, 53.7 [33-71] years; all White). Participants applied a thin coating of their allocated cream to their bilateral extremities once or twice daily. Due to financial burdens, some participants changed from twice to once daily. The lesions were assessed on days 28, 56, and 84 by investigator-standardized photographs, and 93/122 visits were conducted virtually. DSAP severity decreased by 50% in the lovastatin-cholesterol group (from 3.08 [95% CI, 2.57-3.60] to 1.54 (95% CI, 1.04-2.05] points on the DSAP-GASI; P < .001)  and by 51.4% in the lovastatin alone group (from 2.92 [95% CI, 2.40-3.43] to 1.50 [95% CI, 0.99-2.01] points; P < .001). Application frequency did not significantly differ between the two groups. Although no serious adverse events were reported, the most common adverse events were application discomfort (n = 4), myalgia (n = 2), elevation in creatine kinase levels (n = 1), and rash formation (n = 1).  Overall, this randomized clinical trial supports lovastatin cream as a potential new primary treatment for DSAP.

Image: PD

©2023 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.