2. Academic Validation
  3. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2)

Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2)

  • Br J Dermatol. 2021 Mar;184(3):437-449. doi: 10.1111/bjd.19574.
A Wollenberg 1,  A Blauvelt 2,  E Guttman-Yassky 3,  M Worm 4,  C Lynde 5 6,  J-P Lacour 7,  L Spelman 8 9,  N Katoh 10,  H Saeki 11,  Y Poulin 12,  A Lesiak 13,  L Kircik 14 15,  S H Cho 16,  P Herranz 17,  M J Cork 18,  K Peris 19,  L A Steffensen 20,  B Bang 20,  A Kuznetsova 20,  T N Jensen 20,  M L Østerdal 20,  E L Simpson 21,  ECZTRA 1 and ECZTRA 2 study investigators
Affiliations

Affiliations

  • 1 Department of Dermatology and Allergy, Ludwig Maximilian University of Munich, Munich, Germany.
  • 2 Oregon Medical Research Center, Portland, OR, USA.
  • 3 Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 4 Division of Allergy and Immunology, Department of Dermatology, Venereology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
  • 5 Lynde Dermatology, Probity Medical Research, Markham, ON, Canada.
  • 6 Department of Medicine, University of Toronto, Toronto, ON, Canada.
  • 7 Department of Dermatology, University Hospital of Nice, Nice, France.
  • 8 Veracity Clinical Research, Brisbane, QLD, Australia.
  • 9 Probity Medical Research, Woolloongabba, QLD, Australia.
  • 10 Department of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • 11 Department of Dermatology, Nippon Medical School, Tokyo, Japan.
  • 12 Laval University and Centre Dermatologique du Québec Métropolitain and Centre de Recherche Dermatologique du Québec Métropolitain, Québec, QC, Canada.
  • 13 Department of Dermatology and Pediatric and Oncologic Dermatology, Medical University of Łódź, Łódź, Poland.
  • 14 Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 15 Indiana University Medical Center, Indianapolis, IN, USA.
  • 16 Department of Dermatology, The Catholic University of Korea, Seoul, South Korea.
  • 17 Department of Dermatology, Hospital Universitario La Paz, Madrid, Spain.
  • 18 Sheffield Dermatology Research, Department of Infection, Immunity, and Cardiovascular Disease, The University of Sheffield and Sheffield Teaching Hospitals NIHR Clinical Research Facility, Sheffield, UK.
  • 19 Dermatology, Catholic University and Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.
  • 20 LEO Pharma A/S, Ballerup, Denmark.
  • 21 Department of Dermatology, Oregon Health & Science University, Portland, OR, USA.
PMID: 33000465 DOI: 10.1111/bjd.19574
Abstract

Background: Tralokinumab, a fully human monoclonal antibody, specifically neutralizes interleukin-13, a key cytokine driving peripheral inflammation in atopic dermatitis (AD). In phase II studies, tralokinumab combined with topical corticosteroids provided early and sustained improvements in AD signs and symptoms.

Objectives: To evaluate the efficacy and safety of tralokinumab monotherapy in adults with moderate-to-severe AD who had an inadequate response to topical treatments.

Methods: In two 52-week, randomized, double-blind, placebo-controlled, phase III trials, ECZTRA 1 and ECZTRA 2, adults with moderate-to-severe AD were randomized (3 : 1) to subcutaneous tralokinumab 300 mg every 2 weeks (Q2W) or placebo. Primary endpoints were Investigator's Global Assessment (IgA) score of 0 or 1 at week 16 and ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16. Patients achieving an IgA score of 0 or 1 and/or EASI 75 with tralokinumab at week 16 were rerandomized to tralokinumab Q2W or every 4 weeks or placebo, for 36 weeks. The trials were registered with ClinicalTrials.gov: NCT03131648 and NCT03160885.

Results: At week 16, more patients who received tralokinumab vs. placebo achieved an IgA score of 0 or 1: 15·8% vs. 7·1% in ECZTRA 1 [difference 8·6%, 95% confidence interval (CI) 4·1-13·1; P = 0·002] and 22·2% vs. 10·9% in ECZTRA 2 (11·1%, 95% CI 5·8-16·4; P < 0·001) and EASI 75: 25·0% vs. 12·7% (12·1%, 95% CI 6·5-17·7; P < 0·001) and 33·2% vs. 11·4% (21·6%, 95% CI 15·8-27·3; P < 0·001). Early improvements in pruritus, sleep interference, Dermatology Life Quality Index, SCORing Atopic Dermatitis and Patient-Oriented Eczema Measure were observed from the first postbaseline measurements. The majority of week 16 tralokinumab responders maintained response at week 52 with continued tralokinumab treatment without any rescue medication (including topical corticosteroids). Adverse events were reported in 76·4% and 61·5% of patients receiving tralokinumab in ECZTRA 1 and ECZTRA 2, respectively, and in 77·0% and 66·0% of patients receiving placebo in ECZTRA 1 and ECZTRA 2, respectively, in the 16-week initial period.

Conclusions: Tralokinumab monotherapy was superior to placebo at 16 weeks of treatment and was well tolerated up to 52 weeks of treatment.

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