Tralokinumab shows clinical improvement in patients with prurigo nodularis-like phenotype atopic dermatitis: A multicenter, prospective, open-label case series study

Abstract

There are several phenotypes of atopic dermatitis (AD). 1 Girolomoni G. de Bruin-Weller M. Aoki V. et al. Nomenclature and clinical phenotypes of atopic dermatitis. Ther Adv Chronic Dis. 2021; 2620406223211002979 Google Scholar The prurigo nodularis (PN)-like phenotype occurs in nearly one-half of the patients with AD. 1 Girolomoni G. de Bruin-Weller M. Aoki V. et al. Nomenclature and clinical phenotypes of atopic dermatitis. Ther Adv Chronic Dis. 2021; 2620406223211002979 Google Scholar In all AD phenotypes, chronic itch usually leads to an itch-scratch cycle with the development of secondary lesions. These include, in the PN-like phenotype, excoriated hyperkeratotic, intensely itchy papules and nodules in areas accessible to scratch. 1 Girolomoni G. de Bruin-Weller M. Aoki V. et al. Nomenclature and clinical phenotypes of atopic dermatitis. Ther Adv Chronic Dis. 2021; 2620406223211002979 Google Scholar An emergent role of the type 2 cytokines, including interleukin (IL) 4, IL-13, IL-31, and IL-5, has been suggested in the pathogenesis underlying AD itch. IL-13 is a potent enhancer of the neuronal response to different itch stimuli. 2 Miron Y. Miller P.E. Hughes C. et al. Mechanistic insights into the antipruritic effects of lebrikizumab, an anti–IL-13 mAb. J Allergy Clin Immunol. 2022; 150: 690-700 Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar Tralokinumab, a fully human IgG4 monoclonal antibody neutralizing IL-13, is a novel treatment that has demonstrated safety and efficacy in clinical trials in treating adult patients with moderate-to-severe AD. 3 Wollenberg A. Blauvelt A. Guttman-Yassky E. et al. 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; 184: 437-449 Crossref PubMed Scopus (170) Google Scholar In our open-label, retrospective case series study, tralokinumab improved clinical manifestations in 2 patients presenting with PN-like phenotype. 4 Pezzolo E. Naldi L. Tralokinumab in the treatment of resistant atopic dermatitis: an open-label, retrospective case series study. J Eur Acad Dermatol Venereol. 2023; 37: e644-e645 Crossref Scopus (2) Google Scholar Therefore, we prospectively investigated tralokinumab efficacy and safety in treating for at least 16 weeks, 17 adult patients with moderate-to-severe PN-like phenotype AD at 5 dermatology tertiary referral centers, from July 2021 to November 2022. Patients were eligible for treatment with tralokinumab after failing the first-line approved biologic treatment dupilumab, without achieving eczema area and severity index (EASI)-50 after 16 weeks of treatment. Written informed consent was obtained for each patient. At baseline, patients (mean age, 60.75 years; 76.5% women) presented moderate-to-severe PN-like phenotype AD and with means (ranges) EASI of 27.2 (16-45), Investigator Global Assessment (IGA) of 3.7 (3-4), numeric rating scale (NRS)-itch of 9.8 (8-10), NRS-sleeplessness of 8.9 (6-10), and dermatology life and quality index (DLQI) of 16.3 (14-24). Seventy percent of patients used concomitant topical corticosteroids at baseline. Patients reached EASI-50 within 4 weeks, EASI-75 within 12 weeks, and EASI-90 within 32 weeks (mean EASI reduction from 27.2-1.7, P <.001) (Fig 1). The mean NRS-itch and sleeplessness and DLQI values significantly decreased as early as week 4 (P <.001) and progressively reduced after 16-week continuous treatment. Tralokinumab resulted in complete or almost complete clinical remission (IGA 0 or 1) in 76% (13/17) of patients, in 47% (8/17) within week 12, in 23% within week 32, and 6% within week 64, and an at least 2-grade IGA reduction in the others (24%) (Fig 2). Both patients with 16-weeks treatment observation (8/17) and patients with 32 or 64 weeks of continuous treatment (9/17) maintained clinical efficacy without reporting any serious adverse effect. 5 Licata G, Tancredi V, Pezzolo E, et al. Efficacy and safeness of tralokinumab in patients with atopic dermatitis who developed conjunctivitis under dupilumab: a case series. J Eur Acad Dermatol Venereol. Published online April 5, 2023. https://doi.org/10.1111/jdv.19108 Google Scholar Mild conjunctivitis represented the main adverse effect (12%), followed by injection-site reaction, localized urticaria, and mild herpetic stomatitis. Fig 2Atopic dermatitis severity assessed by the Investigator Global Assessment score at different times. IGA, Investigator Global Assessment. View Large Image Figure Viewer Download Hi-res image