Novel systemic therapies in atopic dermatitis: what do we need to fulfil the promise of a treatment revolution?

Abstract

Patients with atopic dermatitis (AD) who do not adequately respond to topical therapy and phototherapy often need systemic immunomodulatory treatment to control their symptoms. Conventional systemic agents, such as ciclosporin, azathioprine, and methotrexate, have been used for decades, but there are concerns about their safety profile. There are now many novel systemic agents emerging through clinical trials, which may have great potential in the treatment of AD. Despite this, there are very few data comparing the performance of these drugs against each other. The purpose of this article is to review the current systemic therapies in AD and present an indirect comparison of systemic AD treatments using effectiveness and safety data from published randomised controlled trials, highlighting important remaining gaps in knowledge. Although the latest developments in systemic AD treatments are exciting and dearly needed, further work is required before the promise of a therapeutic revolution becomes reality.

Dupilumab in Adults with Moderate-to-Severe Atopic Dermatitis and Prior Use of Systemic Non-Steroidal Immunosuppressants: Analysis of Four Phase 3 Trials

“…The similar baseline disease severity between patients with or without prior use of systemic NSISS is likely a consequence of clinical trial entry criteria. In dupilumab phase 3 trials, the AD severity of patients at baseline was similar to that of patients who are candidates for systemic therapy in EU registries (BioDay [34]; EURO-STAD [10]; TREAT [12]). In a retrospective Korean study, baseline severity of disease was higher in NSISS-experienced patients (EASI 31.7 in the prior NSISS group vs. 26.9 in the NSISSnaïve group) [35].…”

“…In addition, registry studies show higher adherence to dupilumab treatment, compared to CsA and methotrexate [34,37]. Ongoing registry studies (EUROSTAD [10]; TREAT [12]) are further investigating long-term response and adherence to systemic treatments.…”

“…Oral corticosteroids (OCS) are unsuitable for chronic or relapsing AD because of high likelihood of disease rebound [9]. Systemic non-steroidal immunosuppressants (NSISS), including cyclosporin A (CsA), methotrexate (MTX), mycophenolate mofetil, and azathioprine, are frequently prescribed to treat severe AD refractory to topical therapy (EUROSTAD [10]; TREAT [11,12]); however, there is a lack of robust evidence from large, well-designed randomized clinical trials (RCT) to support their use, and their toxicity profile requires frequent laboratory monitoring, and long-term treatment is not recommended because of a poor benefit-risk profile [13][14][15][16][17][18]. Patients treated with these broad-spectrum NSISS can suffer relapses and substantial side effects, including nephrotoxicity, liver dysfunction, and an increased risk of infection and cancer, and they are contraindicated in many patients [13,[15][16][17][18][19][20][21][22].…”

The European TREatment of ATopic eczema (TREAT) Registry Taskforce survey: prescribing practices in Europe for phototherapy and systemic therapy in adult patients with moderate‐to‐severe atopic eczema*

“…For years dermatologists have had a small array of available therapies for patients with moderate‐to‐severe atopic eczema (AE) – but no robust guidance for these therapies, as the supporting evidence has been of varying quality and only a few long‐term studies are available 1–5. Currently, the first biologic with a promising efficacy profile, dupilumab, is registered in Europe and the USA for adult and adolescent patients with AE 6–8. However, long‐term safety evidence is missing 9.…”

Shrinkage estimation for dose-response modeling in phase II trials with multiple schedules

“…Atopic dermatitis, the most common form of eczema, is a chronic inflammatory disease that is characterized by skin rash and itching (Mayo Clinic, 2018). Recently, there is an increasing number of clinical trials investigating novel systemic agents for the treatment of atopic dermatitis (Alexander et al, 2019). We consider phase II trials of two human monoclonal antibodies, dupilumab and MOR106, for the treatment of atopic dermatitis.…”