Tralokinumab Plus Topical Corticosteroids in Adults With Severe Atopic Dermatitis and Inadequate Response to or Intolerance of Ciclosporin A

AD, atopic dermatitis; BMI, body mass index; BSA, body surface area; CSA, ciclosporin A; DLQI, Dermatology Life Quality Index; EASI, Eczema Area and Severity Index; NRS, numeric rating scale; POEM, Patient-Oriented Eczema Measure; q2w, every 2 weeks; SCORAD, SCORing Atopic Dermatitis; TCS, topical corticosteroids. Data are provided as median (interquartile range) unless otherwise stated.

CI, confidence interval; CSA, ciclosporin A; DLQI, Dermatology Life Quality Index; EASI, Eczema Area and Severity Index; IGA, Investigator's Global Assessment; N, number of patients; n, number of patients with observation; NRS, numeric rating scale; POEM, Patient-Oriented Eczema Measure; q2w, every 2 weeks; SCORAD, SCORing Atopic Dermatitis; SE, standard error; TCS, topical corticosteroids. ^aMantel–Haenszel risk difference stratified by prior CSA use and baseline IGA. ^bIntercurrent events used: rescue treatment and permanent discontinuation of the investigational medicinal product (neither resulting from the COVID-19 pandemic) and patient onset of the COVID-19 pandemic. ^cPatients who received rescue treatment or permanently discontinued the investigational medicinal product as their first intercurrent event before the analysed visit were considered nonresponders. ^dData collected after patient onset of the COVID-19 pandemic were considered missing. Data missing as a result of the COVID-19 pandemic were imputed using multiple imputation. Missing data that were not attributable to the COVID-19 pandemic were imputed as nonresponse. ^eData collected after permanent discontinuation of the investigational medicinal product, initiation of rescue treatment or patient onset of the COVID-19 pandemic were not included. ^fOutcome measures were produced using least square means with observed margins as weighting. Repeated-measurements model: change from baseline = treatment × week + baseline value × week + prior CSA use + country (Germany: yes/no) + baseline IGA. If no postbaseline scheduled assessments had taken place before any intercurrent event, the last observation was carried forward (baseline included).

CI, confidence interval; CSA, ciclosporin A; EASI, Eczema Area and Severity Index; IGA, Investigator's Global Assessment; N, number of patients; n, number of patients with observation; q2w, every 2 weeks; SE, standard error; TCS, topical corticosteroids. ^aMantel–Haenszel risk difference stratified by prior CSA use and baseline IGA. ^bIntercurrent events used: rescue treatment and permanent discontinuation of the investigational medicinal product (neither resulting from the COVID-19 pandemic) and patient onset of the COVID-19 pandemic. ^cIntercurrent events used: rescue treatment and permanent discontinuation of the investigational medicinal product. Missing data were imputed as nonresponse. ^dCochran–Mantel–Haenszel test stratified by prior CSA use and baseline IGA. ^eCSA treatment failure was defined as inadequate effect after > 12 weeks of exposure or reports of an adverse event related to CSA. ^fData collected after permanent discontinuation of the investigational medicinal product, initiation of rescue treatment or patient onset of the COVID-19 pandemic were not included. ^gData are presented with the assumption that nonreturned tubes were fully used. Outcome measures were produced using least square means with observed margins as weighting. Repeated-measurements model: log[cumulative amount of TCS (g) + 1] = treatment × week + prior CSA use + country (Germany: yes/no) + baseline IGA. If no postbaseline scheduled assessment had taken place before any intercurrent event, the last observation was carried forward (baseline included). Estimates were back-transformed using an exponential function. ^hRatio of means.

%, percentage of patients with one or more event; AD, atopic dermatitis; N, number of patients in the analysis set; n, number of patients with at least one event; PYE, patient-years of exposure; q2w, every 2 weeks; R, rate (number of AEs divided by PYE multiplied by 100); TCS, topical corticosteroids. ^aAEs recorded during the exposure time throughout the treatment period (weeks 0–26) are shown. ^bSerious AEs as preferred terms included appendicitis (one patient in the tralokinumab + TCS group), cerebrovascular accident, seizure, anaphylactic reaction, peripheral nerve injury, squamous cell carcinoma of the skin, depressed mood, suicidal ideation, asthma and AD (five patients in the placebo + TCS group). ^cPreferred term according to the Medical Dictionary for Regulatory Activities version 20.0. ^dIncludes the preferred terms conjunctivitis bacterial, conjunctivitis viral and conjunctivitis allergic.

Authors and Disclosures

J. Gutermuth¹, A.E. Pink², M. Worm³, L. Soldbro⁴, C. Bjerregård Øland⁴ and S. Weidinger<sup>5

1</sup>Department of Dermatology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel (VUB), Brussels, Belgium
²St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, UK
³Division of Allergy and Immunology, Department of Dermatology, Venereology and Allergy, Charité – Universitätsmedizin Berlin, Berlin, Germany
⁴LEO Pharma A/S, Ballerup, Denmark
⁵Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

Correspondence
Stephan Weidinger. Email: sweidinger@dermatology.uni-kiel.de

Conflicts of interest
See Appendix.

J.G., A.E.P. and M.W. are joint first authors.

Sidebar 1

What is Already Known About This Topic?

• Patients with atopic dermatitis (AD) insufficiently controlled with topical therapy have few systemic treatment options, most of which are broadly immunosuppressive, not approved for AD, and associated with commonly recognized toxicities and side-effects.

• Ciclosporin A (CSA) is a systemic immunosuppressant approved for AD in most European countries and Japan, but not all patients respond to treatment.

• Side-effects, including hypertension and renal damage, limit the use of CSA.

Sidebar 2

What Does This Study add?

• In this 26-week, placebo-controlled trial in patients with severe AD (Eczema Area and Severity Index ≥ 20), tralokinumab plus topical corticosteroids (TCS) as needed significantly improved key AD outcomes.

• The ECZTRA 7 trial supports the efficacy and safety of tralokinumab plus TCS as needed in adult European patients with severe AD whose disease was not adequately controlled with CSA or who had contraindications to oral CSA.

Appendix

Conflicts of Interest

J.G. reports honoraria as a consultant/advisory board member/speaker and/or grants from AbbVie, Genzyme, LEO Pharma, Lilly, Pfizer, Regeneron and Sanofi. A.E.P. has acted as an advisor/speaker/investigator for or received educational support from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, La Roche-Posay, LEO Pharma, Lilly, Novartis, Pfizer, Sanofi and UCB. M.W. has served as a scientific advisor and/or clinical trial investigator and/or paid speaker for AbbVie, Aimmune, ALK, Allergopharma, Boehringer Ingelheim, Dermira, Galderma, Janssen, LEO Pharma, Lilly, Mylan, Novartis, Pfizer, Regeneron and Sanofi-Genzyme. L.S. and C.B.Ø. are employees of LEO Pharma. S.W. is coprincipal investigator of the German atopic eczema registry TREATgermany. He has received institutional research grants from La Roche-Posay, LEO Pharma and Sanofi Deutschland GmbH, has performed consultancies for AbbVie, Kymab, LEO Pharma, Lilly, Novartis, Pfizer, Regeneron and Sanofi-Genzyme, has lectured at educational events sponsored by AbbVie, Galderma, LEO Pharma, Novartis, Regeneron and Sanofi-Genzyme, and is involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of psoriasis and atopic eczema.