Efficacy and Safety of Upadacitinib Dose Escalation and Reduction in Adult Patients With Moderate-To-Severe Atopic Dermatitis: Results of a Randomized, Blinded, Treat-To-Target, Multicenter Phase 3b/4 Study (Flex Up)

Melinda Gooderham; Tiago Torres; Shinichi Imafuku; Marius Rademaker; Vimal H Prajapati; Athanasios Tsianakas; Dedee F Murrell; Witold Owczarek; Yu Han; Wan-Ju Lee; Gweneth Levy; Nadia Ibrahim; Alvaro Moreira; Kave Shams

doi:10.1093/bjd/ljaf236

Efficacy and Safety of Upadacitinib Dose Escalation and Reduction in Adult Patients With Moderate-To-Severe Atopic Dermatitis: Results of a Randomized, Blinded, Treat-To-Target, Multicenter Phase 3b/4 Study (Flex Up)

Br J Dermatol. 2025 Jun 23:ljaf236. doi: 10.1093/bjd/ljaf236. Online ahead of print.

Authors

Melinda Gooderham^{1

2}, Tiago Torres³, Shinichi Imafuku⁴, Marius Rademaker⁵, Vimal H Prajapati^{6

7}, Athanasios Tsianakas⁸, Dedee F Murrell⁹, Witold Owczarek¹⁰, Yu Han¹¹, Wan-Ju Lee¹¹, Gweneth Levy¹¹, Nadia Ibrahim¹¹, Alvaro Moreira¹¹, Kave Shams^{12

13}

Affiliations

¹ Queen's University, Kingston, Ontario, Canada.
² SKiN Centre for Dermatology and Probity Medical Research, Peterborough, Ontario, Canada.
³ Centro Hospitalar Universitário de Sto António, University of Porto, Porto, Portugal.
⁴ Fukuoka University Faculty of Medicine, Fukuoka, Japan.
⁵ Clinical Trials New Zealand, Waikato Hospital Campus, Hamilton, New Zealand.
⁶ Skin Health & Wellness Centre, Dermatology Research Institute, and Probity Medical Research, Calgary, Alberta, Canada.
⁷ Division of Dermatology, Department of Medicine and Sections of Community Pediatrics and Pediatric Rheumatology, Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada.
⁸ Fachklinik Bad Bentheim, Bad Bentheim, Germany.
⁹ Faculty of Medicine, University of New South Wales, Sydney, Australia.
¹⁰ Military Institute of Medicine, Warsaw, Poland.
¹¹ AbbVie Inc, North Chicago, Illinois, USA.
¹² Leeds Centre for Dermatology, Chapel Allerton Hospital, Leeds, UK.
¹³ Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom.

PMID: 40581082
DOI: 10.1093/bjd/ljaf236

Abstract

Background: The pivotal clinical trials assessed the efficacy and safety of fixed dose upadacitinib (UPA) 15 mg (UPA15) and 30 mg (UPA30) once-daily (QD) in atopic dermatitis (AD).

Objectives: This randomized, blinded, treat-to-target, multicenter phase 3b/4 study assessed the efficacy and safety of dose escalation to UPA30 and dose reduction to UPA15 based on a clinical response (90% reduction in Eczema Area and Severity Index [EASI 90]) after 12 weeks of treatment in adult patients with moderate-to-severe AD.

Methods: A total of 461 patients were randomized in a 1:1 ratio to receive oral doses of UPA15 (N=229) or UPA30 (N=232) QD during the 12-week double-blinded period. At Week 12, patients on UPA15 not achieving EASI 90 were dose escalated to UPA30 (UPA15/30); patients achieving ≥EASI 90 continued on UPA15 (UPA15/15). Patients on UPA30 not achieving EASI 90 at Week 12 continued on UPA30 (UPA30/30); patients achieving ≥EASI 90 received a reduced dose of UPA15 (UPA30/15) for 12 additional weeks. The primary efficacy endpoint was EASI 90 achievement at Week 24. Results were reported descriptively as observed. Safety outcomes were assessed.

Results: At Week 24, in patients receiving dose escalation (UPA15/30), 48.1%(95%CI: 39.6,56.6) achieved EASI 90, and in patients receiving dose reduction (UPA30/15), 68.5%(95%CI:60.5,76.4) maintained EASI 90. Amongst patients who continued on initial dose, 29.3%(95%CI:19.4,39.1) on UPA30/30 achieved EASI 90, and 74.6%(95%CI:64.5,84.8) on UPA15/15 maintained EASI 90. At Week 24, 32.5%(95%CI:22.5,42.6) and 38.0%(95%CI:28.5,47.5) of patients on UPA15/30 and UPA30/15, respectively, achieved Worst Pruritus Numeric Rating Scale score of 0 or 1 (WP-NRS 0/1), and 20.7%(95%CI:12.0,29.5) and 35.0%(95%CI:25.7,44.3), respectively, achieved combined EASI 90 and WP-NRS 0/1. At Week 24, treatment-emergent adverse events were reported in 43.1%(UPA15/15), 54.2%(UPA15/30), 61.5%(UPA30/30), and 48.9%(UPA30/15) of patients. No malignancies, adjudicated venous thromboembolic events, or deaths were reported.

Conclusion: Treatment of moderate-to-severe AD with UPA15 or UPA30, with dose escalation or dose reduction based on achievement of the optimal treatment target of EASI 90 at Week 12 demonstrate that both treatment approaches support achievement and maintenance of EASI 90 at Week 24. Overall safety findings were consistent with the known UPA safety profile, with no new safety signals identified.