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Introduction <p>Patients with moderate-to-severe atopic dermatitis (AD) who discontinue dupilumab need additional therapeutic options. Lebrikizumab’s distinct mechanism of action may provide that alternative treatment. We evaluated efficacy and safety of lebrikizumab in adults and adolescents with moderate-to-severe AD previously treated with dupilumab.</p> Methods <p>In the open-label ADapt trial, patients who discontinued dupilumab due to inadequate response, adverse events (AEs)/intolerance, or other reasons received lebrikizumab 250-mg every 2&#xa0;weeks (Q2W) following 500-mg loading dose at baseline/week&#xa0;2, through week&#xa0;16, with optional topical therapy. From weeks&#xa0;16–24, responders (≥ 75% improvement in Eczema Area and Severity Index [EASI&#xa0;75] or Investigator’s Global Assessment score 0/1 with ≥ 2-point improvement from baseline) received lebrikizumab every 4&#xa0;weeks; inadequate responders continued lebrikizumab Q2W. The primary endpoint was EASI&#xa0;75 at week&#xa0;16 in the intent-to-treat population; EASI&#xa0;75 was also analyzed by reason for dupilumab discontinuation. Secondary and exploratory efficacy endpoints were assessed throughout.</p> Results <p>Among the 86 patients enrolled, primary reasons for stopping dupilumab were inadequate response (<i>n</i> = 48, 55.8%), AEs/intolerance (<i>n</i> = 14, 16.3%), and other reasons (<i>n</i> = 24, 27.9%). Fifty-nine patients (68.6%) completed week&#xa0;16; 52 patients (60.5%) completed week&#xa0;24. At weeks&#xa0;16 and 24, respectively, response rates were 57.4% (35/61) and 60.0% (33/55) for EASI&#xa0;75; 53.2% (25/47) and 61.5% (24/39) for Pruritus Numeric Rating Scale ≥ 4-point improvement; and 83.0% (44/53) and 83.0% (39/47) for Dermatology Life Quality Index ≥ 4-point improvement. Most treatment-emergent AEs were mild/moderate. Serious AEs and discontinuations due to AEs were reported by 2 (2.3%) and 5 (5.8%) patients, respectively. Of the 10 patients who discontinued dupilumab due to eye-related events, facial dermatitis, or inflammatory arthritis, none reported similar events with lebrikizumab.</p> Conclusion <p>Results suggest that lebrikizumab provides meaningful improvements in skin clearance, itch, and quality of life in dupilumab-experienced patients with moderate-to-severe AD, with a safety profile consistent with other lebrikizumab phase&#xa0;3 trials.</p> Trial Registration. <p>ClinicalTrials.gov identifier, NCT05369403.</p>

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Lebrikizumab Improves Clinical Manifestations, Symptoms, and Quality of Life in Patients with Moderate-to-Severe Atopic Dermatitis Previously Treated with Dupilumab: Results from the ADapt Study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月19日

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  • Jonathan I. Silverberg,
  • Lindsay Ackerman,
  • Jerry Bagel,
  • Linda Stein Gold,
  • Andrew Blauvelt,
  • David Rosmarin,
  • Raj Chovatiya,
  • Matthew Zirwas,
  • Gil Yosipovitch,
  • Jill Waibel,
  • Jenny E. Murase,
  • Ben Lockshin,
  • Jamie Weisman,
  • Amber Reck Atwater,
  • Jennifer Proper,
  • Maria Silk,
  • Evangeline Pierce,
  • Maria Lucia Buziqui Piruzeli,
  • Sonia Montmayeur,
  • Christopher Schuster,
  • Jinglin Zhong,
  • Maria Jose Rueda,
  • Sreekumar Pillai,
  • Eric Simpson

摘要

Introduction

Patients with moderate-to-severe atopic dermatitis (AD) who discontinue dupilumab need additional therapeutic options. Lebrikizumab’s distinct mechanism of action may provide that alternative treatment. We evaluated efficacy and safety of lebrikizumab in adults and adolescents with moderate-to-severe AD previously treated with dupilumab.

Methods

In the open-label ADapt trial, patients who discontinued dupilumab due to inadequate response, adverse events (AEs)/intolerance, or other reasons received lebrikizumab 250-mg every 2 weeks (Q2W) following 500-mg loading dose at baseline/week 2, through week 16, with optional topical therapy. From weeks 16–24, responders (≥ 75% improvement in Eczema Area and Severity Index [EASI 75] or Investigator’s Global Assessment score 0/1 with ≥ 2-point improvement from baseline) received lebrikizumab every 4 weeks; inadequate responders continued lebrikizumab Q2W. The primary endpoint was EASI 75 at week 16 in the intent-to-treat population; EASI 75 was also analyzed by reason for dupilumab discontinuation. Secondary and exploratory efficacy endpoints were assessed throughout.

Results

Among the 86 patients enrolled, primary reasons for stopping dupilumab were inadequate response (n = 48, 55.8%), AEs/intolerance (n = 14, 16.3%), and other reasons (n = 24, 27.9%). Fifty-nine patients (68.6%) completed week 16; 52 patients (60.5%) completed week 24. At weeks 16 and 24, respectively, response rates were 57.4% (35/61) and 60.0% (33/55) for EASI 75; 53.2% (25/47) and 61.5% (24/39) for Pruritus Numeric Rating Scale ≥ 4-point improvement; and 83.0% (44/53) and 83.0% (39/47) for Dermatology Life Quality Index ≥ 4-point improvement. Most treatment-emergent AEs were mild/moderate. Serious AEs and discontinuations due to AEs were reported by 2 (2.3%) and 5 (5.8%) patients, respectively. Of the 10 patients who discontinued dupilumab due to eye-related events, facial dermatitis, or inflammatory arthritis, none reported similar events with lebrikizumab.

Conclusion

Results suggest that lebrikizumab provides meaningful improvements in skin clearance, itch, and quality of life in dupilumab-experienced patients with moderate-to-severe AD, with a safety profile consistent with other lebrikizumab phase 3 trials.

Trial Registration.

ClinicalTrials.gov identifier, NCT05369403.