Trending Now: Pipeline Possibilities for Pediatric Skin Conditions

Dermatology Times, Dermatology Times, February 2022 (Vol. 43. No. 2), Volume 43, Issue 2
Pages: 29

Treatments awaiting FDA approval could bolster the range of nonsteroids and well-tolerated topicals aimed at combating pediatric cutaneous disorders.

Pediatric patients challenged by skin conditions ranging from molluscum contagiosum to inflammatory dermatoses such as psoriasis and atopic dermatitis (AD) could see new solutions within 12 to 24 months, according to Peter Lio, MD, FAAD.

Lio, who is a clinical assistant professor of dermatology and pediatrics at Northwestern University Feinberg School of Medicine in Chicago, Illinois; founding director of the Chicago Integrative Eczema Center; and founding partner of Medical Dermatology Associates of Chicago, walked through some of the advances on the horizon in his presentation on trends in pediatric dermatology at Winter Clinical in Koloa, Hawaii.1

Molluscum Contagiosum

Standard treatments for molluscum contagiosum include cryotherapy, curettage, tape stripping with silk tape, the duct tape method, and the application of topical salicylic acid and cantharidin.

Due to its relatively favorable safety-efficacy balance, Lio said he often chooses topical cantharidin as a first-line therapy. He noted that it is well-tolerated, usually painless, and often improves outcomes when used properly with good guidance in the appropriate patient.

Cantharidin has been used for more than 60 years as a compounded product, he said, but it still is not FDA-approved in the United States. That may change soon.

Lio pointed to results of recent phase 3 studies of a drug–device combination containing cantharidin 0.7% (VP-102; Verrica) that could pave the way for a new standard of treatment for the condition.2 “If everything keeps moving forward, this would be the only FDA-approved product to treat molluscum contagiosum,” Lio said.

It also could be an emerging standard for molluscum treatment, which currently lacks a standard of care, according to the study authors.

This combination product may address some of the challenges associated with treating molluscum with cantharidin, including application, according to the authors.3

VP-102 offers standardization of cantharidin in unit dose vials, allowing direct, controlled application on molluscum, with stable concentration, and good shelf life, the study reported.

Lio rated gentle cryotherapy with liquid nitrogen as his top choice for second-line therapy. While the treatment can be uncomfortable and even leave a scar, it nevertheless remains a very effective treatment approach, he noted. Curettage is also very effective, he said, but can sometimes be somewhat painful, if not traumatic, for the patient and family members.

With a release date predicted for 2022, a nitric oxide releasing topical agent is a new home-treatment approach that may prove to be a welcome treatment option for molluscum contagiosum. The novel agent consists of two components: a gel containing berdazimer sodium co-administered with a hydrogel, resulting in the promotion of nitric oxide release and potential anti-viral activity.

“I think that something that can be applied at home (as opposed to the cantharidin which needs to be applied in the office) has real potential. Some families do not want to keep coming back for treatments, some patients have trepidations about any sort of procedure, and it could even be an adjunctive treatment used in addition to one of the other treatments,” Dr. Lio said. “It is always difficult to compare across studies, but my sense is that this will be a bit less effective than the office-administered treatments, but I think that could be okay if it is gentle.”

Another option is waiting for the condition to resolve.

“For many molluscum patients, it is very reasonable to use the so-called tincture of time: waiting and seeing if it will resolve on its own. However, if it is causing distress, either from things like itch and even an eczematous dermatitis that can develop, or, more commonly, simply due to the stigma of having these infectious bumps in visible areas, it is reasonable to at least discuss treatment,” Lio said.

Patients and their families need to understand how long the wait could be. The largest cohort to date revealed the average duration of infection is 13.3 months and 13% of cases remain unresolved.4

Atopic Dermatitis

The chronic relapsing and remitting inflammatory skin disease is characterized by intensely pruritic skin lesions with repeated scratching triggering a self-perpetuating itch-scratch cycle, which can have significant negative psycho-social consequences and a negative impact on the patient’s quality of life. Topical steroids are the standard of care for AD disease flare-ups, followed by novel topicals including pimecrolimus and tacrolimus ideally used for long-term maintenance. FDA-approved in September 2021, ruxolitinib cream (Opzelura; Incyte) is “a new, exciting topical JAK inhibitor agent that has very recently become available for the treatment of atopic dermatitis,” in Lio’s view.

“I have been very pleased with the efficacy of ruxolitinib cream in the small number of patients under followup so far. It seems to be more powerful than tacrolimus and pimecrolimus for the patients that I have seen who have used one or both of those agents in the past. That is very exciting because I like to minimize the use of steroids when possible and this may be a viable non-steroidal choice for some,” Lio said.

Although ruxolitinib carries a black box and the risks may be real, Lio said that the black box does not give a good sense of how likely such risks are for a given patient. According to Lio, both tacrolimus and pimecrolimus topicals, for instance, have had black box warnings since around 2005 that state:

“Long-term safety of topical calcineurin inhibitors has not been established. Although a causal relationship has not been established, rare cases of malignancy (e.g., skin and lymphoma) have been reported in patients treated with topical calcineurin inhibitors...”

The conclusion of a recent study5 including 10 years data on the use of tacrolimus in children is among the best long-term safety data in dermatology, Lio said. That study found that there is no support for the hypothesis that topical tacrolimus increases long-term cancer risk in children with AD.

“We have this disconnect that the specific medication, when used in this context, does not seem to have a significant risk, making our job very difficult: we never want to be dismissive or undermine a warning like this, but for an actual patient and their family we want to be honest, open, and accurate,” Lio said.

Less is known of topical ruxolitinib as longer-term studies are lacking and oral JAK inhibitors also have similar black box warnings to this topical. Nevertheless, this may be an important new treatment option for some patients once safety and treatment cost of ruxolitinib are appropriately addressed, he added.

Asivatrep is another new and promising treatment option on the horizon for AD. The exciting aspect of this topical medication is that it targets the itch and thus may be safer than other topicals used for AD. In a recent study6, investigators reported that at week 8, significantly more patients in the asivatrep group (36.0%) than in the vehicle group (12.8%) had IGA scores of 0 or 1. The mean ± SD change in the pruritus visual analog scale score at week 8 was -2.3 ± 2.4 for the asivatrep group and -1.5 ± 2.4 for the vehicle group, and no significant safety issues were reported.

Until the oral JAK inhibitors receive approval for AD in the United States, patients with this condition can use dupilumab (Dupixent; Sanofi and Regeneron) or the very recently approved tralokinumab (Adbry, LEO Pharma) for moderate to severe disease. According to Lio, the biologic agents may be more of a "first line systemic" agent for many patients. Both dupilumab and tralokinumab have similar safety profiles and comparable efficacy, and neither requires laboratory monitoring. As they are very targeted anti-inflammatory treatments, they are generally not considered to be immunosuppressants and they do not have black box warnings, Lio said.

“We have many unmet needs in dermatology and especially for our eczema patients. I have a very enriched clinic for patients who have tried and failed a number of other treatments and are suffering very much. So, I think the key is to engage in a shared decision-making process with the patient and family. To discuss the burden of the disease, the different treatment options, what has been tried, and what their treatment goals are,” Lio noted.

“The best therapeutic approaches tend to work on cooling the inflammation, calming the itch, strengthening the skin barrier, and rebalancing the microbiome, and sometimes this can be done with gentle, safe treatments. However, when these gentler approaches fall short and are not enough, more powerful approaches should be considered even in the face of some risk, which needs to be candidly discussed with the patient,” he added.

Oral JAK inhibitors offer the promise of some of the most impressive efficacy data for atopic dermatitis Lio said, although there are some important risks to review and monitor. If they receive FDA approval, these agents may be an extremely important treatment option for those who either cannot use a biologic, who have not benefited enough from one, or for those who have side effects from them.

“There are a tremendous number of new treatments finally being realized. With this also comes a new and deeper understanding of the underlying diseases. Sorting out the nuances of these therapies will take time and experience, but with the right connection among pediatric patients, their families and the clinician, it should be very fruitful,” Lio said.

Disclosures

Lio is a speaker for Sanofi Genzyme, Pfizer, Eli Lilly and Company, LEO Pharma, Galderma, Regeneron Pharmaceuticals, and L’Oréal; serves on the advisory boards of Almirall, ASLAN Pharmaceuticals, Dermavant Sciences, Sanofi Genzyme, Regeneron Pharmaceuticals, Pfizer, LEO Pharmaceuticals, AbbVie, Eli Lilly and Company, Micreos, L’Oreal, Pierre-Fabre, Johnson & Johnson, Level Ex, KPAway, Unilever, Menlo Therapeutics, Theraplex, IntraDerm, Exeltis, AOBiome, Altus Labs, Galderma, Verrica, Arbonne, Amyris, Bodewell, YobeeCare, Burt’s Bees, My-Or Diagnostics, and Kimberley Clark; conducts research for AOBiome, Sanofi Genzyme, Regeneron Pharmaceuticals, and AbbVie; is a patent holder for Theraplex AIM (patent pending); and a stockholder in Micreos, YobeeCare, Altus Labs, KPAway, and LearnSkin.

References:

1. Lio P. What’s new and hot in dermatology. Presented at: 2022 Winter Clinical Dermatology Conference; January 14 to 19, 2022; Koloa, Hawaii, and virtual.

2. Eichenfield L, Hebert A, Mancini A, Rosen T, Weiss J. Therapeutic Approaches and Special Considerations for Treating Molluscum Contagiosum. J Drugs Dermatol. 2021 Nov 1;20(11):1185-1190. doi: 10.36849/jdd.6383. PMID: 34784125.

3. Eichenfield LF, McFalda W, Brabec B, Siegfried E, Kwong P, McBride M, Rieger J, Willson C, Davidson M, Burnett P. Safety and efficacy of VP-102, a proprietary, drug-device combination product containing cantharidin, 0.7% (w/v), in children and adults with molluscum contagiosum: two phase 3 randomized clinical trials. JAMA Dermatol. 2020 Dec 1;156(12):1315-1323. doi: 10.1001/jamadermatol.2020.3238. PMID: 32965495; PMCID: PMC7512131.

4. Olsen JR, Gallacher J, Finlay AY, Piguet V, Francis NA. Time to resolution and effect on quality of life of molluscum contagiosum in children in the UK: a prospective community cohort study. Lancet Infect Dis. 2015 Feb;15(2):190-5. doi: 10.1016/S1473-3099(14)71053-9. Epub 2014 Dec 23. PMID: 25541478.

5. Paller AS, Fölster-Holst R, Chen SC, Diepgen TL, Elmets C, Margolis DJ, Pollock BH. No evidence of increased cancer incidence in children using topical tacrolimus for atopic dermatitis. J Am Acad Dermatol. 2020 Aug;83(2):375-381. doi: 10.1016/j.jaad.2020.03.075. Epub 2020 Apr 1. PMID: 32246968.

6. Chun Wook Park, Beom Joon Kim, Yang Won Lee, et al. Asivatrep, a TRPV1 antagonist, for the topical treatment of atopic dermatitis: Phase 3, randomized, vehicle-controlled study (CAPTAIN-AD) J Allergy Clin Immunol. 2021 Oct 2;S0091-6749(21)01456-1.doi: 10.1016/j.jaci.2021.09.024. Online ahead of print.