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Professor, Department of Pediatrics
Chief, Division of Dermatology
Seattle Children's Hospital
University of Washington School of Medicine
Robert Sidbury, MD, MPH, has disclosed that he has received funds for research support from Galderma, Micreos, Regeneron, and UCB.
General Trends in Atopic Dermatitis
Many poster presentations at the 2021 American Academy of Allergy, Asthma & Immunology (AAAAI) and American Academy of Dermatology (AAD) conferences reflected advances in our understanding of atopic dermatitis (AD) and an explosion in therapeutic targets. In this ClinicalThought, I share my thoughts and takeaways on 4 of the posters presented at the conferences.
Clinical Characterization of Skin Pain in Children With AD
AD affects approximately 13% of children in the United States and is linked to symptoms of itch, rash, and sleep disturbance. I dislike when people say that it is “just” AD, since AD can have a major impact on the quality of life of children and adults with moderate to severe AD. Skin pain is a symptom of AD that I think is overlooked. Healthcare professionals rarely ask about it, and it can result in the conflation of pain with itch.
At AAAAI, Cheng and colleagues presented a cross‑sectional survey characterizing skin pain and the impact it has on the quality of life in children with AD. Skin pain was reported by 44% of children 8 years of age or older and was not trivial, with a median intensity of 6.05 out of 10. Children with symptoms of itch and open skin were more likely to have skin pain, and increased skin pain was associated with a reduced quality of life.
Since skin pain is common in children with AD and affects their quality of life, it is important to ask your patients about it. Similar to how we consider sleep loss and quality-of-life questions when making treatment decisions, I think skin pain will help clarify our treatment directions, too.
Treatment of Patients Experiencing Dupilumab-Associated Facial Redness
Facial redness is a recently noted adverse event affecting approximately 10% of patients with AD receiving dupilumab. This adverse event can be significant, as a recent Journal of American Academy of Dermatology paper reported that 11% of patients discontinued dupilumab due to facial redness. Although discontinuation is generally based on appearance, it can also be from stinging and discomfort.
The causes and risk factors for the facial redness are unknown, but commensal yeast of the genus Malassezia may contribute. At AAD, Song and colleagues presented a retrospective review of 20 adults with AD and dupilumab-associated facial redness who were treated with the azoles itraconazole or fluconazole. Itraconazole, which was administered to 16 patients, led to self-reported improvement in 52%, whereas none of the 4 patients receiving fluconazole reported improvements. Both drugs have similar antifungal activity, so if future studies confirm a difference in efficacy, I think it is likely due to a difference in their secondary effects on proinflammatory cytokines.
Healthcare professionals should inform all patients receiving dupilumab about the possibility of facial redness so that they are not caught by surprise if it occurs. It is also important to explore whether other factors are triggering facial redness, such as contact dermatitis, concomitant rosacea, or alcohol use.
Depth and Rapidity of Response With Abrocitinib and Dupilumab in Patients With Moderate to Severe AD
Oral JAK inhibitors show promise to treat moderate to severe AD in adults, but the depth and rapidity of response are unclear. The phase III JADE COMPARE trial presented by Lio and colleagues at AAAI evaluated the efficacy of the JAK1 inhibitor abrocitinib and the interleukin-4/interleukin-13 inhibitor dupilumab in adult patients with AD using traditional and additional stringent endpoints. Stringent endpoints included ≥90% improvement in Eczema Area and Severity Index from baseline and an Investigator’s Global Assessment score of 0. Although these are difficult criteria to meet in patients with moderate to severe AD, the use of stringent endpoints may help improve evaluation of treatment response and allow for better drug comparisons in future AD trials.
Although both abrocitinib and dupilumab had higher efficacy than placebo, there were no statistical comparisons between the drugs to determine if one was more efficacious. However, abrocitinib seems to meet an important patient need for rapid and effective relief from AD signs and symptoms.
If these results are confirmed, it would be very exciting to have oral abrocitinib available. As a pediatric dermatologist, oral agents are near and dear to my heart because most children do not find the prospect of injections appealing. The only potential downside for oral JAK inhibitors is the likely requirement for blood test monitoring, which is unnecessary for dupilumab.
Ruxolitinib Cream Rapidly Decreases Pruritus in AD
At AAD, Blauvelt and colleagues presented data on the efficacy of the JAK1/2 inhibitor ruxolitinib for pruritus associated with AD. Data were pooled from 2 phase III trials that enrolled patients 12 years of age or older. Patients who received topical ruxolitinib had a significant reduction in pruritus within 36 hours, with some patients having improvement as soon as 12 hours. Efficacy was sustained through the entire 8-week period of observation, which is very exciting. We already have topical agents that target different mechanisms, but the addition of JAK inhibitors to calcineurin inhibitors and phosphodiesterase inhibitors can only be a good thing.
However, we may need to be careful when using ruxolitinib topically to ensure that absorption does not reach unacceptable systemic levels. We have previously seen this with the vitamin D analog calcitriol and calcineurin inhibitors. Some children with AD may also have comorbidities resulting in a skin barrier that is further compromised; for example, children with Netherton syndrome have absorbed high levels of topical agents systemically.
Although the phase III trials in this analysis enrolled patients 12 years of age or older, very few clinical trials for JAK inhibitors have enrolled children, particularly young children. So for the time being, there is no prospect of using JAK inhibitors in young children unless it is off label. I look forward to clinical trials involving young children because we need an alternative to corticosteroids in those patients.
Do you currently specifically ask about skin pain in patients with AD? Answer the polling question and share your thoughts in the comments section below.