Kids with atopy have a genetic tendency to develop allergic diseases such as asthma, eczema and eosinophilic esophagitis (EoE), or inflammation of the esophagus. Their parents know too well the toll atopy takes on their children’s lives. They hear the labored breathing of their child with asthma. They see the rashes that cause relentless itching in their child with eczema. They witness firsthand the difficulty their child with EoE has swallowing.  

Thanks in part to two pediatric clinical trials that enrolled patients at the MUSC Shawn Jenkins Children’s Hospital, more kids with eczema and EoE now have a new treatment option. Dupilumab works by blocking the signaling of cells that drive the inflammation that causes many of the symptoms of these conditions. It had previously been approved for some children with asthma, for children 6 years and older with eczema and for adults, 18 years and older, with EoE. MUSC was also a site for the trial in children age 6 to 12 with eczema.

The two trials helped to expand the age range for which the new treatment was approved to include anyone 6 months or older for eczema/atopic dermatitis and expand the clinical indication to EoE for adolescents and adults.

The MUSC site for the atopic dermatitis trial was led by pediatric dermatologist Lara Wine Lee, M.D., Ph.D., and the MUSC site for EoE was led by pediatric allergist Kelli Williams, M.D.

Dupilumab is injected under the skin – monthly for younger children with moderate-to-severe atopic dermatitis and weekly for adolescents with EoE. The shots are administered at home, either by the patients themselves or by parents. Both Wine Lee and Williams offer to give the first shot in-office so that they can provide training to parents and patients who desire it.

Atopic dermatitis/eczema

Before the approval of dupilumab, the mainstay for eczema treatment had been prescription topical anti-inflammatory medications, but they didn’t work for all children.

For more severe cases, systemic immunosuppressive therapies were available, but they knocked back the immune system as a whole, leaving patients vulnerable to infection. In contrast, dupilumab blocks only the part of the immune system known to be involved in inflammation and allergic responses, providing a more targeted approach.

“Unlike other kinds of medications that take the whole immune system down, dupilumab just gets control of that arm of the immune system that is involved in these diseases,” said Wine Lee. “The approval of dupilumab is really revolutionary in terms of my ability to treat patients with moderate to severe atopic dermatitis.”

Nationwide, the atopic dermatitis trial enrolled 161 children, age 6 months to 6 years, with moderate to severe disease and confirmed that the drug was effective in reducing the severity of disease while showing no new safety concerns in children. The most common side effects seen in both adults and children were irritation at the injection site, eye dryness or irritation and reactivation of oral herpes.

Eosinophilic esophagitis

Dupilumab also offers adolescents and adults with EoE a much-needed treatment option. Traditional approaches to EoE include dietary restrictions and medical management. Teenagers can resist being told what to eat and some find it difficult to comply with dietary restrictions.

“A lot of the treatments before this drug were strict dietary avoidance,” said Williams. “And some teenagers didn't like to do that. It can be difficult and distressing for them because they're in high school; they are eating with their friends, and they just want to fit in. For those reasons, adolescents with EoE are a particularly challenging group to manage.”

The national trial of dupilumab in EoE enrolled a total of 240 patients, 72 of whom were adolescents. Tissue studies showed that the dupilumab markedly reduced the number of inflammatory cells, or eosinophils, characteristic of the disease. Patients administered dupilumab also reported fewer problems swallowing at week 24.  As with atopic dermatitis, the safety profile of dupilumab was similar in adults and teens. The most common adverse effects were injection site irritation as well as upper respiratory tract and herpes infections.

The approval of dupilumab to help to control EoE in adolescents could not only improve their quality of life but lessen the disease’s impact on the rest of their lives, said Williams.

“EoE is a disease that can last a lifetime, but it often starts early in childhood,” she said. “And now that this drug is approved for adolescents, and we can intervene and treat it right when it starts and decrease the inflammation, I think it could change the trajectory and natural history of this disease. It could mean that fewer adults will suffer from the disease or have less-severe disease.”

Making MUSC an attractive site for clinical trials

Williams credits the South Carolina Clinical & Translational Research (SCTR) Institute with helping to make MUSC an attractive clinical trial site for industry sponsors such as Regeneron, which manufactures dupilumab.

“For a big sponsor like Regeneron, you have to cross all your t’s and dot your i’s, and SCTR really helps us get a good handle on moving patients through the trial and following up on good patient care,” she said. “SCTR was really instrumental in making sure that this study was a success at MUSC.”

Williams said she is particularly grateful for the expertise of SCTR study coordinator Natalie Naylon, who kept the trial running smoothly.

SCTR also helped Wine Lee to launch her trial and transition it to study coordinators in the Department of Dermatology.

The importance of pediatric clinical trials

Since most clinical trials are conducted in adults, pediatricians are often left to use their own best judgment about how to adapt approved therapies to kids. Both Wine Lee and Williams agree that pediatric clinical trials are needed to clarify the dosing and safety of drugs approved in adults for use in kids.

“In pediatric dermatology and pediatrics in general, we sometimes prescribe off-label. For example, you have a medication like this one that was previously approved for 6 and up, but you have a 5-year-old, and you just really feel like it’s still the best option,” said Wine Lee. “We had the ability to use it, but now we have the weight of a clinical trial behind us, which provides us greater confidence in its safety and proper dosing in these populations.”

Williams couldn’t agree more.

“Children are a vulnerable population affected by a great deal of chronic disease, whether it be asthma, atopic dermatitis or food allergy,” she said. “Doing clinical research to move the treatments for these diseases forward is crucial for improving the quality of care that we can provide to our patients.”