Long-term Outcomes of New Systemic Agents in Atopic Dermatitis: Drug Survival Analyses and Treatment Patterns in Daily Practice

Authors

DOI:

https://doi.org/10.2340/actadv.v105.41504

Keywords:

Atopic Dermatitis, biologics, Janus Kinases, Daily practice, Drug Survival, treatment patterns

Abstract

In recent years, several new systemic agents (biologics and Janus kinase inhibitors [JAKi]) have been registered for the treatment of moderate-to-severe atopic dermatitis (AD). However, comparisons of real-world drug survival data and insights into treatment patterns of these advanced systemics are limited. Data from a prospective observational single-centre registry were collected from 549 adult AD patients (759 treatment courses) receiving biologics (dupilumab, tralokinumab) or JAKi (abrocitinib, baricitinib, upadacitinib) and analysed using Kaplan–Meier survival curves. Cox regression analyses were used to evaluate predictors of survival. Frequencies and percentages summarized data on the initial and subsequent treatments received, with a Sankey diagram illustrating the switching patterns. The 18-month overall drug survival rates for dupilumab, abrocitinib, upadacitinib, tralokinumab, and baricitinib were 70.0%, 51.5%, 48.4%, 39.4%, and 20.4%, respectively. No significant predictors for drug survival were identified. Dupilumab was the predominant initial treatment (87.2%) and upadacitinib the most frequently used second and third treatment. In the total cohort, 57.9% of patients remained on their initial treatment and 26.8% switched to other treatments. In conclusion, dupilumab showed superior survival rates while baricitinib had the lowest survival rate. Frequent switching highlights the need for biomarkers that predict response to advanced systemic treatments to improve attrition rates.

Downloads

Download data is not yet available.

References

Emerson RM, Williams HC, Allen BR. Severity distribution of atopic dermatitis in the community and its relationship to secondary referral. Br J Dermatol 1998; 139: 73-76.

https://doi.org/10.1046/j.1365-2133.1998.02316.x DOI: https://doi.org/10.1046/j.1365-2133.1998.02316.x

Blauvelt A, de Bruin-Weller M, Gooderham M, Cather JC, Weisman J, Pariser D, et al. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. Lancet 2017; 389: 2287-2303.

https://doi.org/10.1016/S0140-6736(17)31191-1 DOI: https://doi.org/10.1016/S0140-6736(17)31191-1

Gutermuth J, Pink AE, Worm M, Soldbro L, Bjerregård Øland C, Weidinger S. Tralokinumab plus topical corticosteroids in adults with severe atopic dermatitis and inadequate response to or intolerance of ciclosporin A: a placebo-controlled, randomized, phase III clinical trial (ECZTRA 7). Br J Dermatol 2022; 186: 440-452.

https://doi.org/10.1111/bjd.20832 DOI: https://doi.org/10.1111/bjd.20832

Reich K, Kabashima K, Peris K, Silverberg JI, Eichenfield LF, Bieber T, et al. Efficacy and safety of baricitinib combined with topical corticosteroids for treatment of moderate to severe atopic dermatitis: a randomized clinical trial. JAMA Dermatol 2020; 156: 1333-1343.

https://doi.org/10.1001/jamadermatol.2020.3260 DOI: https://doi.org/10.1001/jamadermatol.2020.3260

Reich K, Teixeira HD, de Bruin-Weller M, Bieber T, Soong W, Kabashima K, et al. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up): results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2021; 397: 2169-2181.

https://doi.org/10.1016/S0140-6736(21)00589-4 DOI: https://doi.org/10.1016/S0140-6736(21)00589-4

Silverberg JI, Simpson EL, Thyssen JP, Gooderham M, Chan G, Feeney C, et al. Efficacy and safety of abrocitinib in patients with moderate-to-severe atopic dermatitis: a randomized clinical trial. JAMA Dermatol 2020; 156: 863-873.

https://doi.org/10.1001/jamadermatol.2020.1406 DOI: https://doi.org/10.1001/jamadermatol.2020.1406

Stölzl D, Sander N, Heratizadeh A, Haufe E, Harder I, Abraham S, et al. Real-world data on the effectiveness, safety and drug survival of dupilumab: an analysis from the TREATgermany registry. Br J Dermatol 2022; 187: 1022-1024.

https://doi.org/10.1111/bjd.21794 DOI: https://doi.org/10.1111/bjd.21794

Spekhorst LS, de Graaf M, Zuithoff NPA, van den Reek J, Kamsteeg M, Boesjes CM, et al. Dupilumab drug survival and associated predictors in patients with moderate to severe atopic dermatitis: long-term results from the daily practice BioDay Registry. JAMA Dermatol 2022; 158: 1048-1056.

https://doi.org/10.1001/jamadermatol.2022.3014 DOI: https://doi.org/10.1001/jamadermatol.2022.3014

de Wijs L, Schreurs C, Schlösser A, Nijsten T, Hijnen DJ. Baricitinib for atopic dermatitis patients who responded inadequately to dupilumab treatment: First daily practice results. JEADV Clinical Practice 2022; 1: 364-371.

https://doi.org/10.1002/jvc2.64 DOI: https://doi.org/10.1002/jvc2.64

de Wijs LEM, Bosma AL, Erler NS, Hollestein LM, Gerbens LAA, Middelkamp-Hup MA, et al. Effectiveness of dupilumab treatment in 95 patients with atopic dermatitis: daily practice data. Br J Dermatol 2020; 182: 418-426.

https://doi.org/10.1111/bjd.18179 DOI: https://doi.org/10.1111/bjd.18179

Olydam JI, Schlösser AR, Custurone P, Nijsten TEC, Hijnen D. Real-world effectiveness of abrocitinib treatment in patients with difficult-to-treat atopic dermatitis. J Eur Acad Dermatol Venereol 2023; 37: 2537-2542.

https://doi.org/10.1111/jdv.19378 DOI: https://doi.org/10.1111/jdv.19378

Schlösser AR, Boeijink N, Olydam J, Nijsten TEC, Hijnen D. Upadacitinib treatment in a real-world difficult-to-treat atopic dermatitis patient cohort. J Eur Acad Dermatol Venereol 2024; 38: 384-392.

https://doi.org/10.1111/jdv.19581 DOI: https://doi.org/10.1111/jdv.19581

Schlösser AR, Shareef M, Olydam J, Nijsten TEC, Hijnen DJ. Tralokinumab treatment for patients with moderate-to-severe atopic dermatitis in daily practice. Clin Exp Dermatol 2023; 48: 510-517.

https://doi.org/10.1093/ced/llad038 DOI: https://doi.org/10.1093/ced/llad038

Looijen AEM, van Linschoten RCA, Brugma JD, Hijnen DJ, de Jong PHP, van der Kuy PHM, et al. Digital outcome measurement to improve care for patients with immune-mediated inflammatory diseases: protocol for the IMID Registry. JMIR Res Protoc 2023; 12: e43230.

https://doi.org/10.2196/43230 DOI: https://doi.org/10.2196/43230

NVDV. Conventionele systemische immunosuppressieve therapie CE. NVDV, 2019.

Yiu ZZN, Becher G, Kirby B, Laws P, Reynolds NJ, Smith CH, et al. Drug survival associated with effectiveness and safety of treatment with guselkumab, ixekizumab, secukinumab, ustekinumab, and adalimumab in patients with psoriasis. JAMA Dermatol 2022; 158: 1131-1141.

https://doi.org/10.1001/jamadermatol.2022.2909 DOI: https://doi.org/10.1001/jamadermatol.2022.2909

Edwards, W. (1968). Conservatism in human information processing. In B. Kleinmuntz (Ed.) Formal representation of human judgment (pp. 17–52). New York: Wiley.

Khosravi H, Zhang S, Anderson AM, Ferris LK, Choudhary S, Patton T. Dupilumab drug survival, treatment failures, and insurance approval at a tertiary care center in the United States. J Am Acad Dermatol 2020; 82: 1023-1024.

https://doi.org/10.1016/j.jaad.2019.12.034 DOI: https://doi.org/10.1016/j.jaad.2019.12.034

Wan H, Jia H, Xia T, Zhang D. Comparative efficacy and safety of abrocitinib, baricitinib, and upadacitinib for moderate-to-severe atopic dermatitis: A network meta-analysis. Dermatol Ther 2022; 35: e15636.

https://doi.org/10.1111/dth.15636 DOI: https://doi.org/10.1111/dth.15636

Siegels D, Heratizadeh A, Abraham S, Binnmyr J, Brockow K, Irvine AD, et al. Systemic treatments in the management of atopic dermatitis: A systematic review and meta-analysis. Allergy 2021; 76: 1053-1076.

https://doi.org/10.1111/all.14631 DOI: https://doi.org/10.1111/all.14631

Spekhorst LS, Bakker D, Drylewicz J, Rispens T, Loeff F, Boesjes CM, et al. Patient-centered dupilumab dosing regimen leads to successful dose reduction in persistently controlled atopic dermatitis. Allergy 2022; 77: 3398-3407.

https://doi.org/10.1111/all.15439 DOI: https://doi.org/10.1111/all.15439

Beck LA, Thaçi D, Hamilton JD, Graham NM, Bieber T, Rocklin R, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med 2014; 371: 130-139.

https://doi.org/10.1056/NEJMoa1314768 DOI: https://doi.org/10.1056/NEJMoa1314768

de Bruin-Weller M, Thaçi D, Smith CH, Reich K, Cork MJ, Radin A, et al. Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebo-controlled, randomized phase III clinical trial (LIBERTY AD CAFÉ). Br J Dermatol 2018; 178: 1083-1101.

https://doi.org/10.1111/bjd.16156 DOI: https://doi.org/10.1111/bjd.16156

Hussein YM, Ahmad AS, Ibrahem MM, Elsherbeny HM, Shalaby SM, El-Shal AS, Sabbah NA. Interleukin 13 receptors as biochemical markers in atopic patients. J Investig Allergol Clin Immunol 2011; 21: 101-107.

Paller AS, Siegfried EC, Thaçi D, Wollenberg A, Cork MJ, Arkwright PD, et al. Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: A randomized, double-blinded, placebo-controlled phase 3 trial. J Am Acad Dermatol 2020; 83: 1282-1293.

https://doi.org/10.1016/j.jaad.2020.06.054 DOI: https://doi.org/10.1016/j.jaad.2020.06.054

Popovic B, Breed J, Rees DG, Gardener MJ, Vinall LM, Kemp B, et al. Structural characterisation reveals mechanism of il-13-neutralising monoclonal antibody tralokinumab as inhibition of binding to IL-13Rα1 and IL-13Rα2. J Mol Biol 2017; 429: 208-219.

https://doi.org/10.1016/j.jmb.2016.12.005 DOI: https://doi.org/10.1016/j.jmb.2016.12.005

Simpson EL, Bieber T, Guttman-Yassky E, Beck LA, Blauvelt A, Cork MJ, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med 2016; 375: 2335-2348.

https://doi.org/10.1056/NEJMoa1610020 DOI: https://doi.org/10.1056/NEJMoa1610020

Simpson EL, Paller AS, Siegfried EC, Boguniewicz M, Sher L, Gooderham MJ, et al. Efficacy and safety of dupilumab in adolescents with uncontrolled moderate to severe atopic dermatitis: a phase 3 randomized clinical trial. JAMA Dermatol 2020; 156: 44-56.

https://doi.org/10.1001/jamadermatol.2019.3336 DOI: https://doi.org/10.1001/jamadermatol.2019.3336

Worm M, Simpson EL, Thaçi D, Bissonnette R, Lacour JP, Beissert S, et al. Efficacy and safety of multiple dupilumab dose regimens after initial successful treatment in patients with atopic dermatitis: a randomized clinical trial. JAMA Dermatol 2020; 156: 131-143.

https://doi.org/10.1001/jamadermatol.2019.3617 DOI: https://doi.org/10.1001/jamadermatol.2019.3617

Zhao Y, Wu L, Lu Q, Gao X, Zhu X, Yao X, et al. The efficacy and safety of dupilumab in Chinese patients with moderate-to-severe atopic dermatitis: a randomized, double-blind, placebo-controlled study. Br J Dermatol 2022; 186: 633-641.

https://doi.org/10.1111/bjd.20690 DOI: https://doi.org/10.1111/bjd.20690

De Greef A, Ghislain PD, Bulinckx A, Coster A, de Halleux C, Damsin T, et al. Real-life experience of tralokinumab for the treatment of adult patients with severe atopic dermatitis: a multicentric prospective study. Clin Drug Investig 2023; 43: 299-306.

https://doi.org/10.1007/s40261-023-01258-7 DOI: https://doi.org/10.1007/s40261-023-01258-7

Spekhorst LS, de Graaf M, Loeff F, Zuithoff NPA, Bakker D, Boesjes CM, et al. Association of serum dupilumab levels at 16 weeks with treatment response and adverse effects in patients with atopic dermatitis: a prospective clinical cohort study from the BioDay Registry. JAMA Dermatol 2022; 158: 1409-1413.

https://doi.org/10.1001/jamadermatol.2022.4639 DOI: https://doi.org/10.1001/jamadermatol.2022.4639

Schlösser AR, Bult L, Thelen JC, Thiadens A, Schappin R, Nijsten TEC, et al. Higher prevalence of dupilumab-induced ocular adverse events in atopic dermatitis compared to asthma: A daily practice analysis. Clin Transl Allergy 2024; 14: e12386.

https://doi.org/10.1002/clt2.12386 DOI: https://doi.org/10.1002/clt2.12386

Simpson EL, Sinclair R, Forman S, Wollenberg A, Aschoff R, Cork M, et al. Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet 2020; 396: 255-266.

https://doi.org/10.1016/S0140-6736(20)30732-7 DOI: https://doi.org/10.1016/S0140-6736(20)30732-7

Guttman-Yassky E, Teixeira HD, Simpson EL, Papp KA, Pangan AL, Blauvelt A, et al. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomised controlled phase 3 trials. Lancet 2021; 397: 2151-2168.

https://doi.org/10.1016/S0140-6736(21)00588-2 DOI: https://doi.org/10.1016/S0140-6736(21)00588-2

Ytterberg SR, Bhatt DL, Mikuls TR, Koch GG, Fleischmann R, Rivas JL, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med 2022; 386: 316-326.

https://doi.org/10.1056/NEJMoa2109927 DOI: https://doi.org/10.1056/NEJMoa2109927

Agency EM. European Medicines Agency; [cited 2024 Nov 1]. Available from: URL: https://www.ema.europa.eu/en/homepage.

Published

2025-03-09

How to Cite

Schlosser, A. R., Nijman, L., Schappin, R., Nijsten, T. E., & Hijnen, D. (2025). Long-term Outcomes of New Systemic Agents in Atopic Dermatitis: Drug Survival Analyses and Treatment Patterns in Daily Practice . Acta Dermato-Venereologica, 105, adv41504. https://doi.org/10.2340/actadv.v105.41504

Issue

Section

Articles

Categories