Special Report: Safety, Future Directions, & the Art of Therapy Selection in Atopic Dermatitis

Long-term safety considerations are central to decisions about initiating and continuing advanced systemic therapies in atopic dermatitis.

In this video, host Mona Shahriari, MD, notes that several years of clinical trial and real-world data with upadacitinib now support its use in diverse patient subgroups, including individuals who smoke, use hormonal contraception or hormone replacement therapy, or have cardiovascular risk factors. She stresses that adverse events of special interest—such as malignancy, major adverse cardiovascular events, and venous thromboembolism—must be interpreted in the context of baseline risk inherent to the general and atopic dermatitis populations. Current data suggest that rates of such events with JAK inhibitors in atopic dermatitis appear broadly consistent with background rates, which helps her counsel patients and colleagues with greater confidence.

In this video, part of a 6-part Special Report series on switching therapeutic classes in atopic dermatitis, expert guest Andrew Mastro, MS, PA-C, underscores the importance of correlating real-world evidence, such as the CorEvitas-type data sets, with clinical trial outcomes to validate both efficacy and safety expectations during therapy switches. The discussion then turns to recent long-term safety data for tralokinumab, which report rates of major cardiovascular events, thromboembolism, and malignancy that are comparable to those observed with upadacitinib. Mastro explains that while these findings did not change his personal practice—because he already viewed these agents as viable long-term options—they provide valuable reassurance for clinicians and patients who may have been hesitant about JAK inhibitors. Shahriari distills this into a practical message: if a clinician is comfortable with the long-term safety of tralokinumab, they should feel similarly comfortable with upadacitinib when used in appropriately selected patients.

The segment broadens to address the risk of not treating atopic dermatitis aggressively enough. Shahriari emphasizes that uncontrolled inflammation is not benign and that atopic dermatitis is associated with systemic comorbidities, including cardiovascular disease and other inflammatory conditions. She frequently discusses this with parents of pediatric and adolescent patients who may be reluctant to start systemic therapy, explaining that persistent, moderate to severe disease is unlikely to “just go away” and that appropriately selected systemic treatment may mitigate long-term consequences. Mastro describes the “light bulb” moment when patients realize their disease is more than “just an itchy patch,” and how connecting internal inflammation to external manifestations facilitates acceptance of injectable or oral therapy. The discussion concludes with practical pearls: Mastro reminds clinicians to see “a person in the room with a problem,” not just a diagnosis, and Shahriari offers a simple “ART of medicine” framework—assess burden beyond BSA, pick the right mechanism of action, and track response using AHEAD recommendations.

Relevant disclosures for Shahriari include AbbVie, Apogee, Arcutis, Bristol Myers Squibb, Dermavant, Galderma, Incyte, Johnson & Johnson, LEO, Lilly USA, Novartis, Regeneron, Sanofi-Genzyme, Takeda, UCB, Pfizer, and others. Mastro has no relevant disclosures to report.

References:

Silverberg JI, Gooderham M, Katoh N, et al. Combining treat-to-target principles and shared decision-making: International expert consensus-based recommendations with a novel concept for minimal disease activity criteria in atopic dermatitis. J Eur Acad Dermatol Venereol. 2024;38(11):2139-2148. doi: 10.1111/jdv.20229

Silverberg JI, Bunick CG, Hong HC, et al. Efficacy and safety of upadacitinib versus dupilumab in adults and adolescents with moderate-to-severe atopic dermatitis: week 16 results of an open-label randomized efficacy assessor-blinded head-to-head phase IIIb/IV study (Level Up). Br J Dermatol. 2024;192(1):36-45. doi: 10.1093/bjd/ljae404