Advanced Therapies for Moderate-to-Severe Atopic Dermatitis: Marathon or Sprint?

Authors

  • Wei Jing Loo, BSc, MBBS, MRCP, FRCP Adjunct Professor, University of Western Ontario, London, ON

Abstract

Atopic dermatitis (AD) is a chronic, relapsing and remitting disease that has a substantial impact on the lives of patients and caregivers. While mild AD can be adequately managed with topical therapies, patients with moderate-to-severe AD may require systemic treatment which has traditionally consisted of off-label use of immunosuppressants such as methotrexate, cyclosporine, and azathioprine.

Several advanced therapies that target specific components of the pathophysiological pathway in AD are now available for patients with moderate-to-severe disease. Agents approved in Canada include an anti–interleukin (IL)-4 receptor inhibitor that blocks signalling of both IL-4 and IL-13 (dupilumab), a selective anti–IL-13 monoclonal antibody (tralokinumab), and selective Janus kinase (JAK) inhibitors (abrocitinib and upadacitinib). The introduction of these therapies has greatly improved dermatologists’ ability to tailor treatment strategies based on individual clinical profiles and patient preferences.

Author Biography

Wei Jing Loo, BSc, MBBS, MRCP, FRCP, Adjunct Professor, University of Western Ontario, London, ON

Dr. Wei Jing Loo is the owner and Medical Director of DermEffects, a cutting edge dermatology centre located in London, Ontario. Dr. Loo completed medical school in 1997 with an honours degree from the University of New South Wales in Sydney, Australia. She trained in Internal Medicine and obtained membership in the Royal College of Physicians in the United Kingdom in 1999. She completed her dermatology residency training in Cambridge, United Kingdom and obtained her Certificate of Specialist Training in Dermatology in 2005. She is board certified in Canada and a fellow of the Royal College of Physicians and Surgeons of Canada. She is a member of the Canadian Dermatology Association and American Academy of Dermatology. Dr. Loo is at the forefront of the dynamic field of dermatology, serving as an associate investigator for Probity Medical Research. Dr. Loo is an Adjunct Professor at Western University in Ontario. She enjoys teaching and has published her work in many peer-reviewed journals.

 

References

Langan SM, Irvine AD, Weidinger S. Atopic dermatitis. Lancet. 2020;396:345-360.

Wollenberg A, Kinberger M, Arents B, Aszodi N, Avila Valle G, Barbarot S, Bieber T, Brough HA, Calzavara Pinton P, Christen-Zäch S, Deleuran M. European guideline (EuroGuiDerm) on atopic eczema: Part I–systemic therapy. Journal of the European Academy of Dermatology and Venereology. 2022 Sep;36(9):1409-31.

Simpson EL, Bruin-Weller M, Flohr C, Ardern-Jones MR, Barbarot S, Deleuran M, Bieber T, Vestergaard C, Brown SJ, Cork MJ, Drucker AM. When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council. Journal of the American Academy of Dermatology. 2017 Oct 1;77(4):623-33.

Dodson J, Lio PA. Biologics and small molecule inhibitors: an uppdate in therapies for allergic and immunologic skin diseases. Current Allergy and Asthma Reports. 2022 Nov 8:183-193.

Dupixent® (dupilumab) Product Monograph, Sanofi-Aventis Canada Inc. Published online March 25, 2022. Accessed February 13, 2023. https://pdf.hres.ca/dpd_pm/00065186.PDF.

Adtralza® (tralokinumab) Product Monograph, Leo Pharma Inc. Published online February 3, 2023 Accessed February 13, 2023. https://pdf.hres.ca/dpd_pm/00069461.PDF.

Cibinqo® (abrocitinib) Product Monograph, Pfizer Canada. Published online August 5, 2022. Accessed February 13, 2023. https://pdf.hres.ca/dpd_pm/00067858.PDF.

Rinvoq® (upadacitinib) Product Monograph, AbbVie Corporation. Published online August 2, 2022. Accessed February 13, 2023. https://pdf.hres.ca/dpd_pm/00068075.PDF.

Wollenberg A, Blauvelt A, Guttman-Yassky E, Worm M, Lynde C, Lacour JP, Spelman L, Katoh N, Saeki H, Poulin Y, Lesiak A. 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). British Journal of Dermatology. 2021 Mar 1;184(3):437-49.

Silverberg JI, Toth D, Bieber T, Alexis AF, Elewski BE, Pink AE, Hijnen D, Jensen TN, Bang B, Olsen CK, Kurbasic A. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo-controlled phase III ECZTRA 3 trial. British Journal of Dermatology. 2021 Mar 1;184(3):450-63.

Silverberg JI, Adam DN, Zirwas M, Kalia S, Gutermuth J, Pinter A, Pink AE, Chiricozzi A, Barbarot S, Mark T, Tindberg AM. Tralokinumab Plus Topical Corticosteroids as Needed Provides Progressive and Sustained Efficacy in Adults with Moderate-to-Severe Atopic Dermatitis Over a 32-Week Period: An ECZTRA 3 Post Hoc Analysis. American Journal of Clinical Dermatology. 2022 Jul;23(4):547-59.

Blauvelt A, Langley RG, Lacour JP, Toth D, Laquer V, Beissert S, Wollenberg A, Herranz P, Pink AE, Peris K, Fangel S. Long-term 2-year safety and efficacy of tralokinumab in adults with moderate-to-severe atopic dermatitis: Interim analysis of the ECZTEND open-label extension trial. Journal of the American Academy of Dermatology. 2022 Oct 1;87(4):815-24.

Bieber T. Interleukin-13: targeting an underestimated cytokine in atopic dermatitis. Allergy. 2020 Jan;75(1):54-62.

Tsoi LC, Rodriguez E, Degenhardt F, Baurecht H, Wehkamp U, Volks N, Szymczak S, Swindell WR, Sarkar MK, Raja K, Shao S. Atopic dermatitis is an IL-13–dominant disease with greater molecular heterogeneity compared to psoriasis. Journal of Investigative Dermatology. 2019 Jul 1;139(7):1480-9.

Paternoster L, Standl M, Waage J, Baurecht H, Hotze M, Strachan DP, Curtin JA, Bønnelykke K, Tian C, Takahashi A. Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nat Genet.2015;47:1449-1456.

Ungar B, Garcet S, Gonzalez J, Dhingra N, da Rosa JC, Shemer A, Krueger JG, Suarez-Farinas M, Guttman-Yassky E. An integrated model of atopic dermatitis biomarkers highlights the systemic nature of the disease. Journal of Investigative Dermatology. 2017 Mar 1;137(3):603-13.

Szegedi K, Lutter R, Bos JD, Luiten RM, Kezic S, Middelkamp-Hup MA. Cytokine profiles in interstitial fluid from chronic atopic dermatitis skin. Journal of the European Academy of Dermatology and Venereology. 2015 Nov;29(11):2136-44.

Oh MH, Oh SY, Lu J, Lou H, Myers AC, Zhu Z, Zheng T. TRPA1-dependent pruritus in IL-13–induced chronic atopic dermatitis. The Journal of Immunology. 2013 Dec 1;191(11):5371-82.

Oetjen LK, Mack MR, Feng J, Whelan TM, Niu H, Guo CJ, Chen S, Trier AM, Xu AZ, Tripathi SV, Luo J. Sensory neurons co-opt classical immune signaling pathways to mediate chronic itch. Cell. 2017 Sep 21;171(1):217-28.

Simpson EL, Wollenberg A, Soong W, Steffensen LA, Kurbasic A, Schneider S, Zoidis J, Silverberg JI. Patient-oriented measures for phase 3 studies of tralokinumab for the treatment of atopic dermatitis (ECZTRA 1, 2, and 3). Annals of Allergy, Asthma & Immunology. 2022 Nov 1;129(5):592-604.

Beck LA, Bieber T, Weidinger S, Tauber M, Saeki H, Irvine AD, Eichenfield LF, Werfel T, Arlert P, Jiang L, Røpke M. Tralokinumab treatment improves the skin microbiota by increasing the microbial diversity in adults with moderate-to-severe atopic dermatitis: Analysis of microbial diversity in ECZTRA 1, a randomized controlled trial. Journal of the American Academy of Dermatology. 2022 Dec 5.

Blauvelt A, Lacour JP, Toth D. Two-year maintenance of response with tralokinumab in moderate-to-severe atopic dermatitis: interim analysis of the ECZTEND open-label extension trial [abstract no. 153 plus oral presentation]. In: 30th European Academy of Dermatology and Venereology (EADV) Congress 2021.

Beck LA, Thaçi D, Deleuran M, Blauvelt A, Bissonnette R, de Bruin-Weller M, Hide M, Sher L, Hussain I, Chen Z, Khokhar FA. Dupilumab provides favorable safety and sustained efficacy for up to 3 years in an open-label study of adults with moderate-to-severe atopic dermatitis. American Journal of Clinical Dermatology. 2020 Aug;21:567-77.

Jo CE, Finstad A, Georgakopoulos JR, Piguet V, Yeung J, Drucker AM. Facial and neck erythema associated with dupilumab treatment: a systematic review. Journal of the American Academy of Dermatology. 2021 May 1;84(5):1339-47.

Abduelmula A, Rankin BD, Mufti A, Yeung J, Prajapati VH. Tralokinumab for moderate-to-severe atopic dermatitis in adults. Skin Therapy letter. 2023 Jan;28(1):1-6.

Published

2023-06-01

How to Cite

1.
Loo WJ. Advanced Therapies for Moderate-to-Severe Atopic Dermatitis: Marathon or Sprint?. Can Dermatol Today [Internet]. 2023 Jun. 1 [cited 2024 Nov. 9];4(2):5–11. Available from: https://canadiandermatologytoday.com/article/view/4-2-loo

Issue

Section

Articles