Linda Stein Gold, MD

Understanding the Origins of the Boxed Warning for JAK Inhibitors

Video content above is prompted by the following:

Briefly discuss the FDA boxed warning for the JAK inhibitor class. How did this warning come about, and which adverse events are included?

How do the risks for the adverse events stated in the FDA boxed warning compare with what has been observed in the AD patient population? How do these risks compare with JAK inhibitor use in rheumatoid arthritis?

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Experts discuss the FDA boxed warning for JAK inhibitors, which highlights risks such as venous thromboembolism (VTE), major adverse cardiac events (MACE), and malignancy originating from the ORAL surveillance trial. They compare these risks in the atopic dermatitis (AD) patient population with those seen in rheumatoid arthritis, noting generally lower incidences in patients with AD.

Long-Term Efficacy and Safety of JAK Inhibitors in Atopic Dermatitis

How do the long-term efficacy data compare with other treatment options for AD? What are your thoughts on sustained results achieved with monotherapy?

96-week data showed more patients were able to achieve IGA 0/1 and EASI-75, 90, and 100 with abrocitinib monotherapy than those who added topical therapy.

The 188-week data showed that a high proportion of patients on upadacitinib monotherapy were able to achieve EASI-75 (86.3% and 89%) and vIGA-AD 0/1 (59.5% and 61.8%).

How has the long-term safety of abrocitinib and upadacitinib affected your comfort level of keeping patients on JAK inhibitors long-term to treat AD? Are there certain patient types that might not be appropriate for long-term use?

Incidence rates for malignancy, major adverse cardiac events (MACE), and venous thromboembolism (VTE) remain low but were numerically higher for patients older than 65 years.

Adverse event rates are generally consistent between 100 mg, 200 mg, and variable dose cohorts, with a dose-dependent response for herpes zoster and herpes simplex infections.

Incidence rates for malignancy, MACE, and VTE remain low (≤0.5 patients per 100 patient-years) and generally reflect the background observations of these events in the overall AD population.

Adverse event rates are generally consistent between 15-mg and 30-mg doses (slightly higher herpes zoster rates with 30-mg dose

Experts discuss the long-term efficacy and safety of abrocitinib and upadacitinib in atopic dermatitis (AD), with sustained monotherapy results showing significant improvements in Investigator Global Assessment (IGA), Eczema Area and Severity Index (EASI), and Validated IGA-AD (vIGA-AD) scores. They also consider the safety profiles and potential risks, particularly in older patients, for long-term use of JAK inhibitors.

JAK1 Selective Inhibition and the Impact of Selectivity on Efficacy and Safety

The 2 approved oral JAK inhibitors for AD are selective for JAK1. What is the significance of using a selective JAK inhibitor in AD?

How do these agents differ from nonselective JAK inhibitors used in other disease states?

How does this JAK1 selectivity impact the efficacy and safety of these agents in AD?

Experts discuss the significance of using selective JAK1 inhibitors for atopic dermatitis (AD), noting their targeted action compared with nonselective JAK inhibitors, and how JAK1 selectivity enhances both the efficacy and safety of these agents in treating AD.

The Role of the JAK/STAT Signaling Pathway in Atopic Dermatitis

Briefly describe the JAK/STAT signaling pathway and its role within the immune system.

Which JAK enzymes are involved in the pathogenesis of AD?

How does the JAK/STAT pathway play a role in itch and inflammation?

How do JAK inhibitors specifically work to improve AD symptoms (such as itch) and skin clearance?

Experts discuss the JAK/STAT signaling pathway’s critical role in immune response, highlighting the involvement of JAK enzymes in atopic dermatitis (AD) pathogenesis and how JAK inhibitors effectively reduce itch and inflammation, improving symptoms and skin clearance in AD.

Linda Stein Gold, MD

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