Wart treatments vs placebo

Bernard A. Cohen, MD

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Positive results from studies looking at pipeline treatments for common warts might give pediatricians hope that something simple and nondestructive would magically make warts disappear-never to return.

In June, for example, Verrica Pharmaceuticals (West Chester, Pennsylvania) announced Phase 2 trial results showing 51% of subjects achieved complete clearance of common warts when treated with VP-102, a topical solution of 0.7% cantharidin in a single-use applicator.¹

Although the trial suggests VP-102 was well tolerated with no serious adverse events, treating warts with cantharidin and other options brings up the old wart conundrum: Is treating warts worth the risk when most will vanish on their own and most treatments are only temporary? This is according to Bernard A. Cohen, MD, professor of Pediatrics and Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Cohen and coauthors did a retrospective chart review of pediatric patients with common warts in an outpatient setting, published in 2015 in Pediatric Dermatology. Most of the 214 patients surveyed received some form of therapy, but it wasn’t clear that any form of treatment altered the course of their warts. The researchers found that warts resolved in 65% of children by age 2 years and in 80% by age 4 years, regardless of treatment.²

The findings suggest that counseling without aggressive destructive treatment is reasonable for managing warts in most children, the authors concluded.²

“The bottom line is we didn’t find anything that worked better than placebo,” Cohen says. “I think it’s very important for pediatricians to know that still, at this point, it is unclear if anything works better than placebo to make warts go away permanently.”

To best guide patients and families about whether to treat or not to treat warts, pediatricians should know about the natural history of common warts, according to Cohen.

Most important: Risk of serious complications from warts in otherwise healthy kids is negligible. Yet many treatments for warts are destructive and painful and are more likely to cause complications than the warts themselves, he says.

That’s not to say never treat

Still, Cohen notes that children’s quality of life can suffer when their warts are in places that are visible to others. “I’m not saying you should never treat warts. In fact, if I have patients who come in and the kids insist on it, we do a lot of conservative things,” he says.

Topical salicylic acid agents are among the first-line wart treatments Cohen recommends. He tells patients or parents to titrate the salicylic acid to the point that it doesn’t hurt and children don’t overdo do the treatment.

Years ago, Cohen would freeze, burn, and laser warts off, but says he isn’t a big fan of those options today.

“Occasionally I will use a nondestructive laser to make some of them smaller and less visible, but I do not do painful destructive things that could leave scars in children who cannot give consent themselves,” he says. “It’s important that pediatricians know there are palliative treatment options that are very conservative and not painful, which I think would be OK to do.”

When children are distraught about their warts, the goal is to recommend a nonpainful, not terribly destructive treatment to get the warts to dry out and shrink, while recognizing the chances of getting full resolution without recurrence is very low, according to Cohen.

“I had a kid the other day who came in and had one of these filamentous warts on the side of the nose. Everybody thinks they’ve got boogers in their nose falling out,” Cohen says. “I had the patient use a topical salicylic acid very gently to the point where it dries the wart, and I had the patient twist it and pull it off. It’ll probably come back but it might be a couple of weeks.”

Another option among nondestructive treatments is use of a topical retinoid. There are a number of over-the-counter products that Cohen says can make warts peel off a little bit, become flatter and subtler.

None of these have been shown to definitively make warts go away, but treating with salicylic acid, topical retinoid, or over-the-counter wart products might at least decrease wart size and visibility

There are also treatments that patients might have heard work but lack data to support that they do. Take garlic, for example. “What I tell people about garlic is it reduces the risk of it spreading among members of the same household if you wear garlic around your neck. Who wants to get near you if you have garlic around your neck?” Cohen says.

Pediatricians can lay the groundwork

Pediatricians are in a position when they understand the natural history of warts to advise parents and patients about whether to treat and how best to do it for optimal results.

Part of the care includes having a frank discussion with patients and parents about how today’s treatments haven’t been proven to be better than doing nothing and could carry risks. If patients or parents still insist on treatment, pediatricians could recommend safer options, Cohen says. “I do think pediatricians can play a big role here by counseling patients and treating them with conservative treatments early on, if needed,” Cohen says.

Where warts might be more of an issue and worthy of a referral to a pediatric dermatologist or dermatologist is when children have symptoms related to the warts, including pain, or if the warts are on places such as the head or neck.

Pediatricians who elect to treat sexually active pediatric patients who have genital warts should consider a product such as imiquimod or Condylox gel (podofilox).³ “I don’t routinely use these for genital warts in young children unless they have symptoms from the warts,” he says.

In the end, understanding limitations of wart treatment is key for pediatricians, according to Cohen.

“I do think warts are a rite of passage of childhood,” Cohen says. “If you look at warts, the peak presentation is probably 8 or 10 years and around 16 years. I’m not saying that adults don’t get them but many kids who have had them and have had them go away have had an immunologic response and are not going to get them as adults.”

About the pipeline

Cohen says there is some potential for wart products in clinical trials, including the cantharidin topical VP-102. Researchers studied subjects receiving VP-102 to day 84 with an additional period of follow-up through day 147.

“Secondary endpoints included the percent change from baseline in the number of treatable warts and VP-102 achieved a 51% reduction in the number of warts (28 of 55 warts) compared to baseline by Day 84,” according to Verrica Pharmaceutical’s press release. “The most frequently reported adverse events were application site reactions that are well known, reversible side effects related to the mechanism of action of canptharidin, a blistering agent...”¹

Cohen says with this and other pipeline wart treatments questions remain about whether the drugs work better than placebo and cure warts. He asks what happens when treatment is stopped. Do the warts come back, and what about in the years following treatment?

“We need to see the placebo-controlled trials that drugs work better than placebo and make the warts go away permanently,” he says.

Johns Hopkins residents are beginning to study whether children getting the human papillomavirus (HPV) vaccine has an effect on warts, he says.

References:

1. Verrica Pharmaceuticals. Verrica Pharmaceuticals achieves positive topline results in Phase 2 clinical study of VP-102 in patients with common warts [press release]. Available at: https://investors.verrica.com/news-releases/news-release-details/verrica-pharmaceuticalsachieves-positive-topline-results-phase. Published June 26, 2019. Accessed August 12, 2019. 

2. Kuwabara AM, Rainer BM, Basdag H, Cohen BA. Children with warts: a retrospective study in an outpatient setting. Pediatr Dermatol. 2015;32(5):679-683.

3. Moresi JM, Herbert CR, Cohen BA. Treatment of anogenital warts in children with topical 0.05% podofilox gel and 5% imiquimod cream. Pediatr Dermatol. 2001;18(5):448-450; discussion 452.