Orphan No More: A New Momentum for Pediatric Dermatology

FDA Approvals, A Crash Course

March 28, 2017: The US Food and Drug Administration (FDA) approves dupilumab (Dupixent) in adult patients with moderate-to-severe atopic dermatitis.

Fast forward to March 11, 2019: Dupilumab is given clearance for use in adolescence aged 12-17 years old

Fast forward another year. May 26, 2020: The FDA extends the indication down to children aged 6-11 years old.

Let’s jump back in time once more.

September 25, 2009: The FDA approves ustekinumab (Stelara) for moderate-to-severe forms of psoriasis in adult patients.

October 13, 2017: Ustekinumuab is approved for adolescent patients aged 12 years and older.

July 30, 2020: The biologic receives approval for use in pediatric patients 6-11 years of age.

Children in Need

In the above timelines, there are 2 noted—and quite obvious—patterns. The first is the extension of these biologics for use in younger populations. The second is this notable shift in the pediatric dermatology landscape that has occurred within the past year.

Up until these recent FDA approvals, pediatric dermatologists had few options and strategies to employ in their clinical practice.

For them, the greenlighting of new biologics, like dupilumab and ustekinumab, was certainly music to their ears. After all, it represented a turning point in pediatric care—an affirmation of the promises and potential of its trajectory.

“[This] is huge for us,” said Adnan Mir, MD, Marketing Committee Chair, Society for Pediatric Dermatology, in reference to dupilumab’s approval. “We’ve sort of been working with one hand tied behind our back for decades in the pediatric dermatology community.”

Biologics offer expanded and potentially efficacious options to children who fail to respond to first-line therapies, such as topical medications.

For example, in clinical trial, 2 regimens of dupilumab led to >80% improvements in Eczema Area and Severity Index (EASI) scores, compared with <50% improvements by topical corticosteroids alone.

It may go without saying, then, that the pediatric dermatologist has been provided powerful new tools for their up-to-now limited inventory.

Of course, with any advancement in a medical domain or subspeciality comes a host of considerations, concerns, and questions on both the part of the physician and the patient. The realm of pediatric dermatology is no exception.

Nevertheless, the successes of this past year have signaled to dermatologists who specialize in pediatric care an increase in momentum—as well as a sense that their clinical landscape will no longer remain static, for better or for worse.

Before the Biologics

Prior to the FDA’s approval of these biologics, dermatologists were faced with woefully limited avenues to direct their pediatric patients.

For those children with more severe forms of dermatological conditions, especially in psoriasis or atopic dermatitis, dermatologists had no choice but to either prescribe treatments like topical corticosteroids or more aggressive off-label medications.

After all, without a saving grace or Hail Mary, what could be done?

Mir described the choices he has had to make in his clinical practice.

“My inclination is always to go for aggressive topical therapies first to see how they deal with it,” he said.

And yet, he noted a few barriers that may preclude a patient from experiencing the full benefit of the treatment.

For one, the significant upkeep and overall discomfort can make it difficult for a patient to maintain consistency at home. Additionally, patients may be tasked with keeping track of several topical and oral medications at once.

Other more aggressive medications, like methotrexate or cyclosporine, may elicit wariness from parents uncertain whether to submit their children to such a regimen. Improper dosing can also lead to kidney damage, Mir noted.

In the latest episode of HCPLive’s Derm Discussions, Lisa Swanson, MD, a board-certified pediatric dermatologist based in Boise, Idaho, offered a similar sentiment. In fact, she used an apt analogy to describe her experience of choosing among treatments, particularly in atopic dermatitis.

“I’ve been known to say that picking a systemic treatment for bad atopic dermatitis before we had Dupixent is like a picking a port-a-potty out of a row of port-a-potties,” she said. “You know they’re all going to suck, but you’ve got to pick one when you’ve got to go.”

A Turning Point

Of course, one need not have to choose from port-o-potties. This year alone, the FDA oversaw the expanded indications of ustekinumab for plaque psoriasis, dupilumab for atopic dermatitis, and ixekizumab for psoriasis.

For the dermatologist, these biologics are generally preferable over the previous generation of therapeutics.

“To have something that requires a bit of monitoring here and there but is safe and effective is such a boon to all of us,” Mir said.

Swanson concurred, even citing the use of a biologic like dupilumab as “life-changing.”

This year, the Journal of the American Academy of Dermatology published guidelines on the management of moderate-to-severe pediatric plaque psoriasis. The article, which laid out a proposed treatment algorithm for children, only affirmed the reassuring reports of real-world use of biologics.

Furthermore, in addition to acknowledging that adverse events have been consistent with the randomized clinical trial, they noted no new safety signals—words that may ring favorably for the pediatric dermatologist.

However, the guidelines stressed the need to develop treatment strategies and standards that can keep up with the rapid introduction of these new therapeutic options.

Back to Reality

Despite all the promise and fanfare surrounding biologics, this therapeutic class maintains various barriers and limitations.

First and foremost, dermatologists must still determine whether use of biologics is appropriate given the child’s response to previous treatment, especially to topical therapies, and their clinical history.

Even more, Mir acknowledged that the biggest consideration for parents includes the novelty of these agents. Since several of these biologics have recently begun to be used regularly and widely in clinical practice, there are still unknowns in terms of safety data.

“We’re still in our discovery phase of what can go wrong,” he said, refrencing dupilumab. He emphasized that putting a patient, let alone a young child, on a novel therapy should not be taken lightly; the decision will certainly require conversations with the parents or guardian.

And of course, parents might have ingrained aversion to biologics in the same way they might be averse to steroids or systemic medications.

“I like to believe that they’re going to be safe in the long-term,” Mir said. “But, just thinking about it logically, not all of them are going to be amazing.”

In essence, biologics are a new domain that physicians and patients (and their families) must be willing to tread. While these therapies do show great promise, an element of the unknown nonetheless casts an unmistakable pall over them, and that reality check must factor into the unavoidable physician-patient conversation.

A Year in Review

The approved biologics this year represent a beacon of hope, if nothing else.

While dermatologists like Mir and Swanson express optimism about their efficacy and potential safety in the pediatric population, there is still an understanding that more work needs to be done.

The FDA approvals are not the endgame but rather an indication that pediatric dermatology has picked up a new momentum.

There is an expectation that in the coming years children will have increased access to new therapies—like guselkumab (Tremfya) and brodalumab (Siliq) for psoriasis in younger children and risankizumab (Skyrizi) for atopic dermatitis in adolescents.

After all, whether or not it is obvious, innovation is the lifeblood for the field of pediatric dermatology.

“Just as we always have, pediatric dermatologists are looking for innovative ways to use medications off-label that are developed for other conditions,” Mir noted. He cited the uses of omalizumab (Xolair) and ustekinumab for atopic dermatitis.

“I would consider pediatric dermatology to be an orphan field,” he continued. “And for an orphan field like ours, that’s our best bet to drive innovation. And we’ve continued to do that. We’re just doing our best as a community of researchers to really take the first step in convincing pharmaceutical companies to study their drugs in our population.”

And with the door now opened, there is a chance that pediatric dermatology will enter into the spotlight as an orphan that finally found its 2 feet.