NEW YORK — Over the last year, labeling for a number of anti-inflammatory treatments for dermatologic diseases has been updated to include adolescents as well as young children, and this trend is not likely to end, according to an expert.

In psoriasis, for example, an oral inhibitor of interleukin (IL)-23, icotrokinra, is expected to be a “game changer” for pediatric patients if the anticipated approval in 2026 includes adolescents, according to Lawrence Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital in San Diego.

In a report of phase 3 data of icotrokinra last year, the proportion of adolescents who achieved clear or almost clear skin, defined as 90% skin clearance on the Psoriasis Area and Severity Index (≥ PASI90) or as an investigator global assessment (IGA) score of 0 or 1, exceeded 85%.

In this study, called ICONIC-LEAD, adolescents represented only about 10% of those enrolled, but responses on a single daily oral dose of icotrokinra were higher in the pediatric subgroup than in the overall study population for both PASI90 (88.6% vs 65%) and IGA 0/1 (86.4% vs 74%).

Biologic-Like Efficacy Seen With Oral Drug

In adults or children, “it is the first time we are seeing biologic-like effectiveness with an oral therapy,” Eichenfield said at the 28th Annual Mount Sinai Winter Symposium. The full results of ICONIC-LEAD were recently published in The New England Journal of Medicine.

Icotrokinra, a targeted peptide that blocks the IL-23 receptor, is not a biologic, but Eichenfield predicted that more biologics are coming in dermatology, many of which will include pediatric indications.

In the case of biologics, the IL-13 blockers tralokinumab and lebrikizumab, as well as the IL-31 blocker nemolizumab, are already approved for children aged 12 years or older, but Eichenfield noted that registration trials are underway for younger children.

Expanding the indications for existing biologics to include younger children has been encouraged by the experience with the IL-4/13 blocker dupilumab. Dupilumab has been approved for the treatment of moderate-to-severe atopic dermatitis in children as young as 6 months of age since 2022. This approval was based on phase 3 safety and efficacy studies, but more recent data have linked dupilumab to an “improvement in general health” indirectly related to control of atopic dermatitis, Eichenfield said.

Citing numerous published studies, he said that dupilumab in young children has been associated with a reduced risk for “atopic march,” meaning that children treated with this biologic were significantly less likely later in life to develop asthma, allergic rhinitis, or other diseases associated with a TH2 immune response. Dupilumab has also been associated in recent studies with a reduced risk for sleep disorders and a reduced risk for otitis media.

Moreover, there are now data to address some of the most common concerns expressed by parents when offered dupilumab for the treatment of atopic dermatitis in their young child. In regard to the potential for adversely affecting growth, a recently published observational study found that children with atopic dermatitis treated with vs without dupilumab were less likely to fall below the 5th, 25th, or 50th percentiles (P < .001 for all) for growth.

Dupilumab Appears Safe With Childhood Vaccines

As for fears that a biologic might adversely affect childhood vaccine efficacy, Eichenfield cited a systematic review that was conducted by the American College of Allergy, Asthma and Immunology. The conclusion was that there was no evidence that dupilumab affects the safety or efficacy of vaccines, including live vaccines, in children.

All these studies are observational, but they are consistent with the empirical experience of using biologics off-label, and it is encouraging that there has been more extensive testing of a growing array of biologics in children, Eichenfield indicated.

Yet he cautioned that the FDA “has not changed the verbiage” in regard to biologics and vaccine safety, even for dupilumab, let alone biologics not yet approved in young children, even if he, himself, refers to the published studies when counseling patients in shared decision-making discussions.

For children, the recent effort to better characterize the optimal duration of treatment is another area that might change practice in the near term. Interest in prolonged responses to lebrikizumab was prompted by a re-randomization studyof patients with atopic dermatitis. In a 16-week efficacy trial, participating patients, including some patients younger than 18 years, were assigned to lebrikizumab in an every 2-week schedule, to an every 4-week schedule, or to stop therapy.

At 52 weeks, 60% of those in the withdrawal arm vs approximately 70% of those in the two treatment arms maintained an Eczema Area and Severity Index clearance score of 75% or greater.

Although more data are needed, Eichenfield, reporting his own experience, agreed that some proportion of patients appear to do well off therapy for extended periods. In some cases, the return of disease activity after a period off treatment is sufficiently mild that it can be managed with topical therapies.

With further study, he speculated that it might be possible to develop protocols for discontinuation and, if needed, restarting biologics to reduce the burden of chronic courses.

Reactive Infectious Mucocutaneous Eruption (RIME) Requires Systemic Anti-inflammatory Drugs

The number of JAK inhibitors, both oral and systemic, available to children with atopic dermatitis or other inflammatory skin diseases is expected to increase on the basis of numerous ongoing studies, but Eichenfield turned his attention to the potential role of these and other systemic anti-inflammatory drugs in children presenting with RIME.

RIME, a relatively recently described entity, can have an alarming presentation that resembles Stevens-Johnson syndrome. Several articles, including a recent narrative review, suggest that RIME is most closely associated with Mycoplasma pneumoniae infection, but this is not the sole trigger.

Presenting a pediatric case in which RIME was traced to a parainfluenza in a child who had been treated for RIME due to mycoplasma only 6 months earlier, Eichenfield reported that up to 25% of patients have recurrences, often multiple times and not necessarily from the same infection.

“It is essential to treat the infection, but anti-inflammatory therapies are needed,” he said, acknowledging that the first-line therapy is not well established even if both oral JAK inhibitors and injectable TNF inhibitors have been effective in case reports.

Asked to comment about when to consider biologics in children with atopic dermatitis, the senior author of a review article, JiaDe Yu, MD, chair of the Department of Dermatology at Virginia Commonwealth University School of Medicine, Richmond, Virginia, said that he is also encouraged by the potential for new biologic approvals for young children with atopic dermatitis.

“In my experience, about 20%-30% of children fail dupilumab either due to an inadequate response or side effects, such as conjunctivitis and head and neck dermatitis,” he said. For atopic dermatitis, he pointed out that dupilumab is the only systemic therapy of any kind available for children younger than 12 years.

“We have no other effective and safe systemic options for these patients. Having another approved biologic for children with eczema under 12 would give these kids another option,” said Yu. He suspects that the benefits of these medications will prove to outweigh their risks even if data are needed to confirm their role in routine care.

Eichenfield reported having financial relationships with AbbVie, Amgen, Apogee, Arcutis, Attovia, Bausch, Bristol Myers Squibb, Castle, Dermata, Dermavant, Forte, Galderma, Incyte, Janssen, Krystal, Leo, Lilly, Novartis, Otsuka, Pfizer, Regeneron, Sanofi, and UCB. Yu reported having financial relationships with AbbVie, Arcutis, Astria, Dermavant, iRhythm, Kiehl/L’Oreal, Leo, Lilly, Pfizer, Sanofi, SmartPractice, and Sol-Gel.