Systemic treatments for atopic dermatitis: Weighing effectiveness against risks

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Created On: 17/04/2025

Atopic dermatitis (AD) is more than just an inflammatory skin condition—it’s a chronic struggle for many. While multiple systemic treatments exist, their relative effectiveness and safety remain inconclusive. Hence, this systematic review and network meta-analysis sought out to decode the benefits and risks of systemic therapies for AD.

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Key take away

While high-dose upadacitinib leads in effectiveness, it also poses the greatest safety risks. Low-dose upadacitinib and high-dose abrocitinib show efficacy with safety concerns. Dupilumab, lebrikizumab, and tralokinumab offer moderate effectiveness with a safer profile in patients with atopic dermatitis.

Background

Method

As part of the 2023 AD guidelines by leading allergy and immunology organizations, researchers scoured CENTRAL, GREAT, EMBASE, Web of Science, and MEDLINE databases. Randomized trials examining systemic treatments and phototherapy for AD were included. With a rigorous screening process, paired reviewers independently assessed studies, extracted key data, and evaluated bias. A network meta-analysis provided a head-to-head comparison of treatments, assessing AD severity, itch, sleep disturbance, quality of life, flare frequency, and safety concerns. The GRADE framework guided evidence certainty.

Result

A total of 149 trials involving 28,686 patients suffering from moderate-to-severe AD assessed 75 different treatments. High-certainty evidence identified high-dose upadacitinib as one of the most efficient treatments for 5 out of 6 key patient outcomes but also among the most associated with adverse events. High-dose abrocitinib and low-dose upadacitinib were also highly beneficial for 2 outcomes but carried significant risks.

Among biologics, dupilumab, lebrikizumab, and tralokinumab portrayed intermediate effectiveness with a favorable safety profile, though they modestly escalated conjunctivitis risk. Low-dose baricitinib was among the least efficient. The effectiveness and safety of phototherapy, mycophenolate, azathioprine, cyclosporine, oral corticosteroids, methotrexate, and various emerging therapies remain uncertain.

Conclusion

For those with moderate-to-severe AD, the trade-offs are clear: high-dose upadacitinib stands out in effectiveness but comes with safety risks. Low-dose upadacitinib and high-dose abrocitinib follow a similar pattern. Meanwhile, dupilumab, lebrikizumab, and tralokinumab offer a balanced approach—moderate efficacy with a safer profile.