Topical ionic contraviral therapy decreased the size of cutaneous warts caused by human papillomavirus virus (HPV) by a mean of 3 mm, a significant improvement compared with placebo, in a proof-of-concept study, Dr. Melanie Rijsbergen and her associates reported in the British Journal of Dermatology.
The Dr. Rijsbergen of the Center for Human Drug Research, Leiden, the Netherlands, and her coauthors wrote.
“It has been shown that DNA viruses, such as HPV, rely on potassium influx ... for replication. The cardiac glycoside digoxin and loop diuretic furosemide both inhibit potassium influx by interacting with the cell membrane ion cotransporters,” they said, noting that in 2006, an in vitro study found that “the inhibitory effect on DNA replication was most potent when digoxin and furosemide were combined.”
The placebo-controlled phase 2a trial randomized 80 patients with at least two plantar or common warts to one of four arms: digoxin 0.125% plus furosemide 0.125%; digoxin 0.125%; furosemide 0.125%; or placebo applied once a day for 42 consecutive days. A subset of 20 warts underwent histopathology and immunohistochemistry. In all, 139 warts were treated.
Patients were a mean of 26 years old and had developed warts a mean of 6 years before study onset. They had a mean of three warts each; about half were common and half were plantar.
In an analysis of all treated warts, each active treatment conferred a significant benefit, compared with placebo. The combination treatment was the most effective, with a mean diameter reduction of 3 mm. Warts exposed to digoxin alone or furosemide alone showed a mean reduction of about 2 mm.
At the study’s end, primary wart clearance rates were similar in all treatment groups – around 15%. None of the primary warts in the placebo group cleared. Common warts were more responsive to treatment than were plantar warts (24%-27% vs. 8%-15%). “The increased treatment resistance of plantar warts was previously described and seems to be mainly due to callus formation resulting in a decrease in cutaneous permeability of a drug,” the authors wrote.
The HPV viral load decreased by 94% in warts exposed to the combination therapy – a significant benefit, compared with placebo.
There were no discontinuations because of adverse events, and no serious adverse events related to treatment. There was no topical irritation associated with the treatment.
One author is an employee of Cutanea Life Sciences, which funded the study. Dr. Rijsbergen and the remaining authors declared no financial conflicts.
SOURCE: Rijsbergen M et al. Br J Dermatol. 2018 Dec 22. doi: 10.1111/bjd.17583.