Switching from Biologics to Upadacitinib Yields Progressive Improvements in Moderate to Severe AD

Patients with moderate to severe atopic dermatitis (AD) who transitioned from biologic therapy to upadacitinib experienced progressive improvements in skin clearance, itch, and patient-reported symptom control over 9 months, according to real-world data presented in a poster at the 2026 Revolutionizing Atopic Dermatitis (RAD) meeting in Nashville, Tennessee.¹ Findings from the TARGET-DERM Atopic Dermatitis Registry suggest that switching to the oral Janus kinase (JAK) 1 inhibitor may provide meaningful clinical benefit for patients with persistent disease activity following biologic treatment.

Study Overview and Methodology

RAD co-chair, Jonathan I. Silverberg, MD, PhD, MPH, and colleagues conducted an observational, longitudinal analysis of adolescents and adults with AD enrolled in the TARGET-DERM registry in the US and Canada. The investigators sought to evaluate outcomes among patients who discontinued dupilumab or tralokinumab and subsequently initiated upadacitinib in routine clinical practice.

Although biologic therapies have transformed AD management, a subset of patients ultimately require treatment changes because of inadequate response, waning efficacy, or treatment-related adverse events. However, real-world evidence describing outcomes after switching to upadacitinib has remained limited.

The analysis included 148 patients aged 12 years or older who had prior biologic exposure before initiating upadacitinib. Of the 4,636 patients enrolled in the registry, 174 switched to upadacitinib following advanced systemic therapy; 148 met inclusion criteria for this analysis, including 130 patients previously treated with dupilumab and 18 who had received tralokinumab.

Baseline Therapy and Disease Burden

Patients were followed for approximately 9 months after initiating therapy, with outcomes assessed at baseline, 3 months, and 9 months. Most patients (92%) received the 15-mg dose of upadacitinib, and switching generally occurred promptly after discontinuing biologic therapy. More than 70% initiated upadacitinib within 4 weeks of stopping their biologic agent, while nearly 93% transitioned directly without receiving another systemic therapy during the interval.

The cohort demonstrated considerable residual disease burden at the time of switching. At baseline, nearly two-thirds of evaluable patients (65.4%) had moderate to severe disease according to the validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD), while 68.0% reported significant symptoms on the Patient-Oriented Eczema Measure (POEM). Pruritus remained a prominent complaint, with 80.3% reporting a Worst Itch Numeric Rating Scale (NRS) score of 4 or higher before initiating upadacitinib.

Clinical and Patient-Reported Outcomes

Investigators evaluated several stringent treatment targets, including achievement of clear or almost clear skin (vIGA-AD 0/1), complete clearance of affected body surface area (BSA 0%), minimal itch (Worst Itch NRS 0/1), and minimal patient-reported symptoms (POEM 0-2). Across all primary endpoints, the proportion of patients achieving optimal outcomes increased steadily throughout follow-up. The percentage of patients reaching vIGA-AD 0/1 rose from 16.3% at treatment initiation to 43.1% after 3 months and 53.5% by 9 months. Likewise, complete skin clearance, defined as BSA involvement of 0%, increased from 4.8% at baseline to 20.0% at 3 months and 34.9% after 9 months.

Patient-reported improvements followed a similar trajectory. The proportion of patients reporting little or no itch (Worst Itch NRS 0/1) increased from just 2.6% at baseline to 15.4% at 3 months and 34.8% at 9 months. Similarly, the percentage achieving minimal eczema symptoms on the POEM (score 0-2) increased from 10.7% at baseline to 22.2% after 3 months and 36.6% at the final assessment.

Additional supportive outcomes reinforced these findings. Nearly 70% of patients achieved vIGA scores of 2 or less by 9 months, while more than half reported clinically meaningful reductions in itch severity, defined as Worst Itch NRS scores of 4 or lower. Improvements were also observed in sleep quality, skin pain, and dermatology-specific quality of life. At the conclusion of the study, 69.0% of evaluable patients reported minimal or no skin pain, while approximately half achieved minimal sleep disturbance. More than half of patients with available data experienced at least a 4-point improvement in Dermatology Life Quality Index (DLQI) scores.

Study Limitations and Conclusion

The investigators noted that clinician-reported and patient-reported outcomes demonstrated consistent improvement throughout the observation period, suggesting that objective disease control translated into meaningful symptom relief and functional benefit. As an observational registry analysis, the study carries limitations, including variable sample sizes at follow-up visits and reliance on observed-case analyses without formal safety assessment. Nevertheless, the findings provide valuable real-world evidence complementing randomized clinical trial data for upadacitinib.

Silverberg and the authors concluded that switching from biologic therapy to upadacitinib was associated with progressively increasing rates of optimal skin clearance, itch relief, and overall symptom control through nine months. Improvements were observed across both physician-assessed and patient-reported outcomes, including sleep, skin pain, and quality of life, supporting upadacitinib as an effective treatment option for patients with moderate-to-severe AD requiring a change from prior biologic therapy.

Reference

1. Silverberg J, Grada A, Calimlim B, et al. Switching from Biologic Therapy to Upadacitinib in Atopic Dermatitis: Optimal Skin and Symptom Outcomes from the TARGET-DERM Atopic Dermatitis Registry. Presented at the Revolutionizing Atopic Dermatitis (RAD) Conference. June 17-19, 2026. Nashville, Tennessee.