Amy Paller, MS, MD, ‘81, ‘83 GME, distinguished chair and Walter J. Hamlin Professor of Dermatology at Northwestern University, served as the senior author of a pivotal study published in JAMA Dermatology that is shaping the future of treatment for severe skin conditions.
In a groundbreaking analysis led by Northwestern Medicine, researchers have identified that in adolescents suffering from moderate to severe atopic dermatitis, a Janus kinase (JAK)-selective inhibitor can sustain significant symptom relief and enhance quality of life for up to 76 weeks, demonstrating robust evidence for its safety. This critical study is based on comprehensive data from three international and randomized clinical trials.
Over the last five years, several innovative systemic treatment options for atopic dermatitis have been introduced: subcutaneously administered monoclonal antibodies offer targeted therapy, while JAK inhibitors present a novel oral treatment approach. However, concerns about the safety of earlier generations of JAK inhibitors, which led to an FDA boxed warning, have lingered, as the long-term safety profile of newer, more-selective JAK inhibitors remains to be fully understood.
“Adolescents with moderate to severe atopic dermatitis currently have access to five FDA-approved treatment options. Studies indicate that upadacitinib offers the most rapid and effective results among these therapies. Our study rigorously assessed the long-term safety of this treatment—a vital consideration, as adolescents are likely to remain on upadacitinib for extended periods,” remarked Amy Paller, MS, MD, ‘81, ‘83 GME, the proactive chair and Walter J. Hamlin Professor of Dermatology, and senior author of this noteworthy study.
Atopic dermatitis, commonly referred to as eczema, manifests as skin inflammation accompanied by relentless itching. The condition often begins in infancy, yet many adolescents with moderate to severe eczema suffer persistent symptoms into adulthood. The visible rashes and pervasive itch can severely detract from a patient’s overall quality of life, turning daily activities into challenging endeavors.
Approximately 40 percent of adolescents with atopic dermatitis endure moderate to severe symptoms that cannot be adequately managed with topical medications, including corticosteroids. According to Paller, this population needs more effective intervention strategies.
“Historically, we relied primarily on systemic immunosuppressants, which pose significant risk of side effects, or time-consuming phototherapy options that place a strain on adolescents and their families. Today, injected biologics are the new standard for systemic therapy, targeting the activated immune pathways that contribute to atopic dermatitis. Yet, the frequent injection schedule every two weeks presents its own challenges, and at times, biologic therapies may not achieve sufficient effectiveness,” explained Paller. She also holds a professorship in Pediatrics in the Division of Dermatology and serves as director of the Skin Biology and Diseases Resource-Based Center.
Recently, JAK1-selective inhibitors have gained FDA approval for treating adolescents with moderate to severe dermatitis, revolutionizing the therapeutic landscape.
“JAK inhibitors not only greatly alleviate skin inflammation but also rapidly alleviate itching sensations. JAK1 is integral to the immune response that leads to both inflammation and itch in atopic dermatitis. Therefore, the introduction of a JAK inhibitor enables a direct attack on these two debilitating symptoms,” Paller elaborated, highlighting the dual benefits of the treatment.
In their current study, Paller and her research team meticulously examined data from three pivotal international randomized clinical trials, namely Measure Up 1, Measure Up 2, and AD Up. Collectively, these trials encompassed 542 adolescent participants between the ages of 12 and 17 diagnosed with moderate to severe atopic dermatitis. During the initial 16 weeks, these adolescents were administered the JAK1 inhibitor upadacitinib, once daily, either in doses of 15 or 30 milligrams, in conjunction with topical corticosteroids or a placebo. Following this phase, all participants continued with upadacitinib for an additional 60 weeks.
The analysis revealed that those receiving upadacitinib exhibited marked improvement in their symptoms compared to those given a placebo during the initial 16 weeks, as indicated by the Eczema Area and Severity Index Score (EASI-75), along with the Validated Investigator Global Assessment for Atopic Dermatitis and Worst Pruritus Numerical Rating Scale (WP-NRS). Importantly, this positive response was sustained throughout the extended treatment period of 60 weeks without reporting any new adverse effects related to long-term use of the medication.
The findings strongly suggest that upadacitinib could serve as a viable second-line treatment option for patients grappling with moderate to severe disease who do not see adequate results from topical or injectable medications or cannot manage the frequent injections associated with more targeted therapies.
“As we continue to gather substantial evidence regarding the safety of the JAK1-selective inhibitor, we may consider its use earlier in treatment regimens for adolescents. This medication’s swift action, significant reduction of itch, and convenient oral administration could redefine care for this patient demographic. For adolescents who struggle with adherence to greasy topical treatments, having an easily manageable medication can be transformative,” Paller concluded, shedding light on potential shifts in treatment strategies for eczema.
This important research was supported by AbbVie.
**Interview with Dr. Amy Paller on Groundbreaking Research in Atopic Dermatitis Treatment**
*Interviewer:* Thank you for joining us today, Dr. Paller. Your recent study published in JAMA Dermatology has garnered significant attention. Could you summarize the main findings and their implications for adolescents suffering from atopic dermatitis?
*Dr. Paller:* Thank you for having me. Our study revealed that the use of a Janus kinase (JAK)-selective inhibitor, specifically upadacitinib, can provide sustained symptom relief for adolescents with moderate to severe atopic dermatitis for up to 76 weeks. This is not just exciting in terms of clinical efficacy; it also shows a robust safety profile, which is critically important for a population that may need ongoing treatment.
*Interviewer:* That’s impressive. Can you explain why this is a pivotal moment for treating atopic dermatitis, particularly in adolescents?
*Dr. Paller:* Indeed. Adolescents with moderate to severe eczema face daily challenges due to persistent itching and skin inflammation. Until recently, treatment options were limited and often came with significant side effects. Our findings suggest that JAK inhibitors can effectively and quickly alleviate both inflammation and itching, addressing two core symptoms of the disease simultaneously.
*Interviewer:* You’ve highlighted concerns regarding the safety of earlier generations of JAK inhibitors. How does your research mitigate those concerns?
*Dr. Paller:* Absolutely. Our study meticulously analyzed data from three large international randomized clinical trials. By demonstrating long-term safety and efficacy with upadacitinib, we offer solid evidence that can reassure both clinicians and patients. It’s vital that we find treatments that adolescents can rely on for extended periods without compromising their health.
*Interviewer:* With multiple treatment options now available, how do you see the role of JAK inhibitors in the broader context of atopic dermatitis therapy?
*Dr. Paller:* JAK inhibitors represent a significant advancement in our arsenal against atopic dermatitis. While injected biologics are effective, they often require frequent administration and may not provide sufficient relief for every patient. JAK inhibitors offer an oral treatment option that can simplify adherence and improve quality of life for many adolescents.
*Interviewer:* What message would you like to convey to families dealing with adolescent atopic dermatitis?
*Dr. Paller:* I want families to know that there is hope. With ongoing research and new treatment options like JAK inhibitors, we are making strides in managing this challenging condition. If your child is suffering, speak to your dermatologist about the most effective and up-to-date treatment strategies that can significantly improve their quality of life.
*Interviewer:* Thank you, Dr. Paller, for your insights and for sharing the importance of this breakthrough in treating atopic dermatitis.
*Dr. Paller:* Thank you for the opportunity to discuss this vital topic. It’s an exciting time for dermatology, and I’m optimistic about the future of treatment for our adolescents.
