Peter Lio, MD 

boxed warnings on all currently approved JAK inhibitors, as well as the commonly used treatments in dermatology that have boxed warnings.

Boxed Warnings for JAK Inhibitors in AD

This is a video synopsis/summary of a panel discussion involving Christopher Bunick, MD, PhD; Peter Lio, MD; Lisa Swanson, MD, PhD; and Alexandra Golant, MD.

The FDA has introduced a new boxed warning for all currently approved Janus kinase (JAK) inhibitors, including a topical drug, used in the treatment of arthritis and inflammatory conditions. This decision follows findings from the oral surveillance study, which compared tofacitinib with tumor necrosis factor alpha inhibitors in rheumatoid arthritis patients aged 50 and older with at least 1 cardiovascular risk factor. Dr Golant explains that the study involved an extremely immunosuppressed population, which may not be representative of the dermatology patient population.

The boxed warning for JAK inhibitors resulted from the study's failure to meet non-inferiority criteria, leading to concerns about cardiovascular events, mortality, serious infections, malignancy, and thromboembolic events. Dr. Swanson emphasizes the importance of counseling dermatology patients effectively, considering the differences in the study population and the medications specifically designed for dermatological conditions.

Dr Lio adds perspective, stating that a boxed warning does not necessarily mean avoiding the drug's use. He draws parallels with other commonly used medications in dermatology, such as topical tacrolimus and biologics, which also carry boxed warnings. The conversation extends to Dr Swanson's study comparing JAK inhibitors with traditional systemic immunosuppressants like methotrexate and corticosteroids. The study revealed higher risk factors for the latter, prompting Dr Lio to advocate for reconsidering the use of systemic corticosteroids in atopic dermatitis patients.

Dr Lio also praises Dr. Swanson's research for comparing risk factors across different treatments, emphasizing the need for long-term data to continue reassuring clinicians about the safety of JAK inhibitors. Dr Swanson acknowledges the ongoing "JAK journey" and stresses the importance of obtaining more data over time.

In conclusion, the physicians encourage embracing the boxed warning, emphasizing the powerful impact of JAK inhibitors on changing patients' lives. They advocate for thorough yet efficient communication with patients, considering individual medical histories and candidacy for these therapies. Overall, they express confidence in the continued integration and acceptance of JAK inhibitors in dermatological practice.

Video synopsis is AI-generated and reviewed by HCPLive editorial staff.

Videos

Alexandra Golant, MD, comments on the boxed warnings on all currently approved JAK inhibitors, as well as the commonly used treatments in dermatology that have boxed warnings.

safety data of the current JAK inhibitors approved for AD, highlighting adverse events and long-term safety data.

Safety of JAK Inhibitors Approved for AD Treatment

In this discussion about the treatment considerations in atopic dermatitis, the focus shifts from efficacy to safety, particularly regarding Janus kinase (JAK) inhibitors. Dr Lio acknowledges the initial apprehension clinicians and patients might feel due to the black box warning associated with all JAK inhibitors. The warning highlights concerns such as major adverse cardiovascular events, increased mortality, potential clot risks, and malignancy.

Dr Lio emphasizes the need to address these concerns transparently with patients while providing perspective. He notes that the black box warning originated from a study on a specific JAK inhibitor, tofacitinib, in a different population (rheumatoid arthritis patients over 50 with cardiovascular risk factors), making it somewhat less directly applicable to atopic dermatitis patients.

Despite the warning, the conversation shifts to the actual safety profile observed in trials. Dr BunicK discusses common treatment-emergent adverse events, including JAK inhibitor-related acne and the necessity of lab monitoring. Overall, the class has been well-tolerated, and adverse events are mostly theoretical or mild.

The dialogue extends to long-term safety data, with a focus on upadacitinib and abrocitinib. The physicians find the data reassuring, highlighting low rates of severe side effects. They stress the importance of contextualizing the risks, mentioning that the adverse event of highest frequency is shingles, which could potentially be mitigated by vaccination.

The conversation concludes with insights into counseling patients using long-term safety data. Dr Lio and Dr Bunick emphasize the need to understand the patient's individual health context, referencing factors such as oral contraceptives and smoking. They also stress the importance of comparing event rates to baseline rates in the overall population and the rate of the disease without therapy, providing a comprehensive understanding of the risks and benefits associated with JAK inhibitors.

Expert dermatologists review the safety data of the current JAK inhibitors approved for AD, highlighting adverse events and long-term safety data.

Indications and Efficacy of JAK Inhibitors for AD

Lisa Swanson, MD, PhD, discusses FDA-approved topical and systemic Janus kinase (JAK) inhibitors for atopic dermatitis, addressing their indications and clinical trial data. Topically, ruxolitinib is approved for patients aged 12 and older with nonsegmental vitiligo or mild to moderate atopic dermatitis, demonstrating significant efficacy at 8 weeks. Orally, abrocitinib and upadacitinib are daily pills for patients aged 12 and older, with flexible dosing based on response.

Clinical trial data, including the TRuE-AD1 and TRuE-AD2 trials for ruxolitinib and studies comparing upadacitinib and abrocitinib to dupilumab, is reviewed. Ruxolitinib shows rapid efficacy, with about half of the patients achieving IGA (investigator lobal assessment scale) clear or almost clear at 8 weeks. Comparisons with dupilumab reveal that upadacitinib at 100mg is as effective, while the 200mg dose appears slightly more effective. In head-to-head studies, upadacitinib at 30mg outperforms dupilumab.

Dr Swanson also mentions the ongoing Level Up study comparing upadacitinib 15mg to dupilumab and discusses network meta-analyses evaluating advanced therapies. Despite challenges in indirect comparisons, these analyses suggest that upadacitinib at 30mg is superior to upadacitinib at 15mg, which is superior to abrocitinib at 200mg, and abrocitinib at 200mg is superior to dupilumab at 300mg every two weeks.

The discussion concludes with the analogy of treating atopic dermatitis as the Olympics, where JAK inhibitors, specifically abrocitinib and upadacitinib at certain doses, take gold, silver, and bronze, reflecting the revolutionary efficacy and impact on itch in the field.

Lisa Swanson, MD, PhD, reviews the indications for ruxolitinib, abrocitinib, and upadacitinib, as well as the clinical trial data on efficacy of these JAK inhibitors when treating AD.

Differentiating JAK Inhibitors From Other Therapies in AD

Dr Peter Lio, MD, discusses the distinguishing features of JAK (Janus kinase) inhibitors in the context of treating atopic dermatitis. He emphasizes 2 significant aspects that set JAK inhibitors apart from other therapies. Firstly, in the realm of systemic treatments, where there were limited approved options until recently, biologic agents targeting specific cytokines required subcutaneous injections and had a slower onset. In contrast, JAK inhibitors, administered orally, exhibit a remarkably rapid response within hours to days, offering a level of disease control that surpasses previous treatments.

The focus on itch as a crucial aspect of atopic dermatitis treatment is highlighted. Dr Lio refers to a study published in the British Journal of Dermatology, revealing the substantial improvement in quality of life for patients achieving an itch level of zero or 1. The conversation emphasizes the need to address itch comprehensively, not just focusing on skin signs. Achieving itch scores of zero or 1 is identified as a crucial goal for optimal patient outcomes.

The discussion underscores the transformative impact of JAK inhibitors in the field, offering a new tool that informs a "treat to target" approach. The ability to aim for zero itch, coupled with the rapid efficacy of JAK inhibitors, has raised the standards for treating atopic dermatitis. The conversation among the experts reflects a consensus that JAK inhibitors have elevated the efficacy bar, not only in terms of skin clearance but also in addressing itch and improving overall quality of life for patients. The introduction of these inhibitors has empowered clinicians to ask different questions and strive for a higher standard of care, ultimately benefiting patients with atopic dermatitis.

Expert dermatologists discuss the factors that differentiate JAK inhibitors from other AD therapies, highlighting itch scores as they relate to quality of life.

Peter Lio, MD

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