Long-awaited oral therapy for moderate-to-severe AD

There is an urgent need for a non-steroid oral therapy for patients, particularly paediatric patients, with severe atopic dermatitis (AD). Small molecules could be the solution.

A couple of small molecules are in the pipeline for moderate-to-severe AD, such as several Janus kinase (JAK) inhibitors, began Prof. Thomas Bieber (University Medical Center Bonn, Germany) in his presentation [1]. In a phase 2b trial, the selective JAK1 inhibitor upadacitinib showed promising results [2]. Patients inadequately controlled by topical treatment, or for whom topical treatments were not medically advisable were randomised to once-daily upadacitinib monotherapy in 3 doses or placebo. The primary endpoint of this study was the mean percentage improvement in Eczema Area and Severity Index (EASI) score from baseline to week 16. At week 16, all upadacitinib dose groups experienced statistically significant improvements compared with placebo. Mean EASI scores improved 23% for placebo vs 74.4% for the 30 mg dose upadacitinib over the 16-week trial. Upadacitinib was also effective with regard to a couple of key secondary endpoints such as EASI 75 or EASI 90 response, or clear or almost clear skin according to investigator´s global assessment (IGA 0/1). Already after 2 weeks, the agent showed a rapid onset of action with significant differences compared with placebo. It also had a rapid antipruritic effect.

A recent phase 2 study showed a similar efficacy of the JAK1/2 inhibitor baricitinib in patients with moderate-to-severe AD [3]. At week 16, 61% of patients treated with 4 mg baricitinib and topical corticosteroids achieved an EASI 50 response compared with 37% with placebo. The agent showed rapid improvements in EASI, itch, and sleep disturbance with significant improvements seen as early as week 1. Baricitinib is currently approved for rheumatoid arthritis. “At the moment, most of the experiences with JAK inhibitors are in rheumatoid arthritis patients. We do not know whether we will see the same side-effect profile in a dermatologic population,” said Prof. Bieber.

Prof. Bieber concluded that there will be a competition between biologics and JAK inhibitors in the systemic treatment of AD. An advantage of the JAK inhibitors is their rapid onset of action and rapid itch control. Whereas biologics have a very good risk/benefit ratio, JAK inhibitors offer only an acceptable risk/benefit ratio and a narrow therapeutic window. The possibility of the oral intake will lead to a good acceptance, especially in paediatrics.

1 Bieber T. 24th World Congress of Dermatology, 10-15 June 2019, Milan, Italy.

2 Guttman-Yassky E. Abstract 6533, AAD, 16-20 February 2018, San Diego, USA.

3 Guttman-Yassky E, et al. J Am Acad Dermatol 2019;80:913-921.