Conference summaries

Atopic dermatitis

New and emerging therapies in atopic dermatitis

Presented by: Prof. Dagmar Simon Department of Dermatology, Inselspital, Bern University Hospital, Bern, Switzerland
  • Targeted therapies have provided new insights into the pathogenesis of AD.
  • Dupilumab (moderate to severe) and crisaborole (mild to moderate) have been approved for treatment of atopic dermatitis, increasing the range of treatment options
  • JAK inhibition through topical delivery is a highly promising therapy for AD.

With an increasing prevalence during the past decades, atopic dermatitis is a chronically relapsing inflammatory skin condition. Although not completely understood, its pathogenesis is complex and seems to result from a combination of genetic and environmental factors that include skin barrier dysfunction, cutaneous and systemic immune dysregulation, skin microbiota dysbiosis and a strong genetic influence. Not unexpectedly, atopic dermatitis is burdensome for individuals with the disease, their families and society.

  • Management of AD must consider the individual clinical variability of the disease.
  • The aims of therapy are to reduce pruritus and establishing persistent disease control that is sufficient to enable patients to be fully functional.
  • Hence, a multistep approach with interventions aimed at avoiding relevant triggers, improving the skin barrier, normalising skin dysbiosis and reducing inflammation, is mandatory.
  • Therapy is chosen based on disease severity.
  • Basic therapy consists of educational programs, emollients, bath oils and avoidance of clinically relevant triggers.
  • Mild and moderate disease is treated with anti-inflammatory topical therapy, while the latter also consists of proactive therapy with the addition of topical tacrolimus or glucocorticosteroids in many cases.
  • Systemic therapy is reserved for severe cases.
  • In any approach undertaken, it is of utmost importance to make every effort to ensure patient compliance to therapy, while individualising treatment according to the profile and needs of each patient.
  • The pathophysiology of atopic dermatitis is complex and multifactorial, involving elements of barrier dysfunction, alterations in cell mediated immune responses, IgE mediated hypersensitivity and environmental factors.
  • Recent improvements in the understanding of atopic dermatitis have allowed for more rational utilisation of several targeted agents in therapy.
  • Many biologics and small molecule antagonists are in phase 2 and phase 3 trials targeting different pathways, including Th2 immune response, JAK signalling and itch mediators, among others.


  • Dupilumab targets the IL-4/IL-13 receptor, and the results of two phase 3 trials of dupilumab vs. placebo have shown that it leads to significant improvement of the clinical symptoms of atopic dermatitis, as well as significant improvement in the quality of life. [1]
  • More recently, the long-term efficacy and safety of dupilumab with medium-potency topical corticosteroids versus placebo with topical corticosteroids in adults with moderate-to-severe atopic dermatitis has been evaluated. [2]
  • Importantly, week 52 results were similar to those at week 16, indicating that the treatment is long-lasting in patients with response to therapy.
  • The safety profile was also acceptable, although treatment-associated conjunctivitis is seen in about 25-30% of patients. [3]
  • Phase 3 studies are underway for dupilumab in paediatric atopic dermatitis.


  • Lebrikizumab and tralokinumab are two new targeted agents that block the activity of IL-13.
  • Recent studies with both these agents have reported promising results, with improvements in disease severity and favourable safety profiles. [4]
  • In considering blockage of other interleukins, the antibody fezakinumab blocks the activity of IL-22, which promotes epidermal hyperplasia and inhibits skin barrier function.
  • This agent has been studied in a phase 2 trial, which documented significant improvement in SCORAD that was particularly relevant in those with severe disease. [5]
  • However, the results on this trial are limited by its small size and lack of assessment with Eczema Area and Severity Index.


  • The efficacy and safety of nemolizumab, a humanised antibody against IL-31 receptor A, have also been assessed in a recent phase 2 trial for treatment of atopic dermatitis. [6]
  • At week 12, among the patients who received nemolizumab every 4 weeks, changes on the pruritus visual-analogue scale were -43.7% in the 0.1-mg group, -59.8% in the 0.5-mg group and -63.1% in the 2.0-mg group, versus -20.9% in the placebo group (P <0.01 for all comparisons).
  • Changes in the EASI were -23.0%, -42.3% and -40.9%, respectively, in the nemolizumab groups, versus -26.6% in the placebo group.
  • Thus, nemolizumab at all monthly doses significantly improved pruritus in patients with moderate-to-severe atopic dermatitis, which showed the efficacy of targeting IL-31 receptor A.
  • Of note, nemolizumab was also associated with improvements in sleep disturbance.
  • Several JAK inhibitors are in development as oral therapies for moderate-to-severe atopic dermatitis or as topical treatments for mild-to-moderate atopic dermatitis.
  • JAK inhibitors block a range of cytokines, growth factors and/or hormone receptor signalling pathways depending on their relative specificity


  • The results of topical treatment with tofacitinib have been examined in a phase 2 trial. [7]
  • The mean percentage change from baseline at week 4 in EASI score was significantly greater for tofacitinib (-81.7%) vs. vehicle (-29.9%).
  • Patients treated with tofacitinib showed significant improvements vs. vehicle across all prespecified efficacy end points and for pruritus at week 4.
  • Significant improvements in EASI, PGA and BSA were observed by week 1 and improvements in pruritus were observed by day 2.


  • Baricitinib is a JAK1/2 inhibitor that has shown efficacy in atopic dermatitis in phase 2 trial where significantly more patients who received baricitinib, 4 mg, achieved EASI-50 than did patients receiving placebo (61% vs 37%) at 16 weeks. [8]
  • One limitation of this trial was that topical corticosteroids were applied before baricitinib, limiting the ability to compare results with those of baricitinib monotherapy.


  • Crisaborole is a phosphodiesterase 4 inhibitor that has been investigated in two phase 3 studies in atopic dermatitis in an ointment formulation. [9]
  • After 28 days of treatment, more crisaborole- than vehicle-treated patients achieved ISGA score success (clear/almost clear with ≥2-grade improvement; AD-301: 32.8% vs 25.4%, P = 0.038; AD-302: 31.4% vs 18.0%, P <0.001), with a greater percentage with clear/almost clear (51.7% vs 40.6%, P = 0.005; 48.5% vs 29.7%, P <0.001).
  • Crisaborole has now been approved by the EMA and FDA for moderate atopic dermatitis in patients >2 years of age.
  • Targeted therapies have provided new insights in the pathogenesis of AD.
  • JAK inhibition through topical delivery is potentially a promising therapeutic target for AD.

Key messages/Clinical perspectives

  • The targeted therapies dupilumab (moderate to severe) and crisaborole (mild to moderate) have been approved for treatment of atopic dermatitis.
  • Phase 3 studies are ongoing with other targeted therapies for atopic dermatitis.



  1. Simpson EL, Bieber T, Guttman-Yassky E, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016 Dec 15;375(24):2335-48.
  2. Blauvelt A, de Bruin-Weller M, Gooderham M, 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 Jun 10;389(10086):2287-303.
  3. Aszodi N, Thurau, S, Seegraber, et al. Management der Dupilumab‐assoziierten Konjunktivitis beim atopischen Ekzem, JDDG. 2019:17(5):488-92.
  4. Simpson EL, Flohr C, Eichenfield LF, et al. Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: A randomized, placebo-controlled phase II trial (TREBLE). J Am Acad Dermatol. 2018 May;78(5):863-71.
  5. Guttman-Yassky E, Brunner PM, Neumann AU, et al. Efficacy and safety of fezakinumab (an IL-22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments: A randomized, double-blind, phase 2a trial. J Am Acad Dermatol. 2018 May;78(5):872-81.
  6. Ruzicka T, Hanifin JM1, Furue M, et al. Anti-interleukin-31 receptor A antibody for atopic dermatitis. N Engl J Med. 2017 Mar 2;376(9):826-35.
  7. Bissonnette R, Papp KA, Poulin Y, et al. Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial. Br J Dermatol. 2016 Nov;175(5):902-11.
  8. Guttman-Yassky E, Silverberg JI, Nemoto O, et al. Baricitinib in adult patients with moderate-to-severe atopic dermatitis: A phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study. J Am Acad Dermatol. 2019 Apr;80(4):913-21.
  9. Paller AS, Tom WL, Lebwohl MG, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. 2016 Sep;75(3):494-503.

Presenter disclosure information: D Simon: None disclosed.

Medical writer: Patrick Moore, PhD

Reviewer: Martina Lambertini, MD

Local reviewers: Martina Lambertini, MD (Italian); Alain Brassard, MD (French); Jorge Moreno González, MD (Spanish); Swen Malte John, MD, PhD (German); Marcelo Arnone, MD (Portuguese)

Scientific Editor: Prof. Brigitte Dréno, MD



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Presented by: Prof. Kristian Reich, Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, and Skinflammation® Center, Hamburg, Germany


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