Systemic treatment for pediatric atopic dermatitis (AD) has evolved rapidly, moving beyond traditional immunosuppressants to include biologics and oral JAK inhibitors, both of which offer better efficacy and tolerability. Phototherapy also remains an option, although logistical and financial hurdles can limit its long-term use.

It is an exciting time to be thinking about systemic therapy for children with AD. Just a couple of years ago, we did not have great options for treating these patients. We relied primarily on traditional systemic immunosuppressive medications such as cyclosporine and methotrexate. These therapies work for some patients, but there are challenges associated with their use, primarily their side-effect profiles and the constant laboratory work that is needed.

<br>

With the recent US Food and Drug Administration (FDA) approvals, we now have systemic biologic medications for children with AD as young as 6 months of age. Dupilumab, the first biologic to be FDA approved for AD, was a game changer because now we had a drug with really good clinical data and a good safety profile. Because dupilumab can be prescribed for very young patients, this opened the door to thinking about what the long-term impact would be if we were to adequately control AD early on. For example, could it somehow modify the disease course? Is there a possibility that patients could be taken off the drug once their disease has been well controlled for a period and then managed with topicals moving forward? These are the questions that parents and caregivers are going to and will often ask.

<br>

The monoclonal antibodies tralokinumab, lebrikizumab, and nemolizumab are FDA approved for children as young as 12 and are alternatives for patients who cannot be on dupilumab. We know that dupilumab, tralokinumab, and lebrikizumab all work by inhibiting IL-13, and dupilumab also inhibits IL-4. Nemolizumab, the most recently approved biologic for AD, has a different mechanism of action (ie, IL-31 inhibition) and works well for itch.

<br>

JAK inhibitors are taken orally, which is an advantage for patients who do not like receiving a needle every 2 or 4 weeks. Abrocitinib and upadacitinib are FDA-approved oral JAK inhibitors for children as young as 12 and are dosed once per day. They have good clinical trial data supporting their safety and efficacy. Questions remain, however. For example: Can we use JAK inhibitors to control the disease but then transition to a different type of therapy with a slightly better safety profile, or can JAK inhibitors be used intermittently on an as-needed basis?

<br>

In my experience, most patients tolerate oral JAK inhibitors fairly well, particularly younger patients, but JAK inhibitor use is associated with risk of herpetic infections, particularly shingles. Moreover, blood work monitoring is important for patients on JAK inhibitors, as there are FDA boxed warnings for these agents about major adverse cardiovascular events, serious infections, thrombosis, malignancy, and mortality. However, these warnings are primarily based on the results of the ORAL Surveillance study, which was done in a rheumatoid arthritis population aged 50 years or older with cardiovascular risk factors. More recent studies have observed that the rates of these events in patients with AD treated with oral JAK inhibitors are similar to the rates observed in the general population, which is reassuring, in a way.

<br>

Finally, phototherapy may be an option for patients with AD of any age if they can comply with instructions and are able to tolerate the treatment. Phototherapy may also be a big time commitment for some patients and/or their caregivers in terms of requiring patients to come into the office 2 to 3 times per week for several months at a time, which can be difficult due to time constraints. Moreover, we are still determining the optimal frequency and duration for both initial therapy and maintenance therapy with phototherapy for AD. There are also financial constraints influencing phototherapy use because not all insurance plans cover phototherapy, and, even if it is covered, the co-pays can be high and may be unsustainable for everyone long-term—and we need more data to evaluate its efficacy long-term.