Special Report: Inadequate Response and When to Switch Systemic Therapy in Atopic Dermatitis

Determining when to maintain, optimize, or switch systemic therapy in atopic dermatitis requires a nuanced understanding of treatment targets, patient expectations, and evolving evidence.

In this video, expert guest Andrew Mastro, MS, PA-C, describes his approach to defining inadequate response by integrating objective thresholds and patient-reported outcomes. He views a failure to achieve deeper responses—such as EASI 90, IGA 0/1, and near-complete itch control (NRS 0–1)—by approximately 4 months on a biologic as a signal that optimal targets have not been met, especially for moderate to severe disease. He distinguishes primary failure (never achieving moderate or deeper levels of response) from secondary failure (loss of previously adequate control, increased flares, or greater day-to-day disease awareness) and emphasizes that patient dissatisfaction must accompany clinician concern for a switch to be appropriate.

In this video, part of a 6-part Special Report series on switching therapeutic classes in atopic dermatitis, host Mona Shahriari, MD, builds on this framework with a discussion of therapeutic inertia and the importance of not remaining indefinitely at “good enough.” She notes that while some patients may justify longer trial periods, such as 9 months, the AHEAD recommendations explicitly suggest considering a switch if treat-to-target goals are not achieved within 3 to 6 months. Shahriari likens earlier efficacy benchmarks to “first-generation robots” that were impressive at the time but limited in capability; in contrast, contemporary data support aiming for EASI 90 or even EASI 100 and near-complete itch suppression to meaningfully improve quality of life, sleep, and psychosocial outcomes.

A key evidence base discussed is the LEVEL UP study, which evaluated switching from dupilumab to upadacitinib. Shahriari describes the two-period design, beginning with a head-to-head comparison of upadacitinib and dupilumab, where upadacitinib demonstrated superiority at week 16 on a composite endpoint of EASI 90 plus near-complete itch control. The second phase focused on patients with inadequate response to dupilumab (defined as not reaching EASI 75) who then switched to upadacitinib 15 mg. Remarkably, within 4 weeks of switching, nearly 7 in 10 of these prior nonresponders achieved EASI 75, about one-third reached EASI 90, and many had started from a baseline of roughly EASI 50 at the time of switch. These findings reinforce that failure on one advanced therapy does not preclude robust response to another mechanism of action.

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