ICD 2021: Novel drug shows promise in atopic dermatitis, says Professor Dedee Murrell


A drug initially developed for ulcerative colitis has shown promise as an itch-reducing, quality of life-improving treatment for atopic dermatitis, according to research presented by Professor Dedee Murrell at the International Congress of Dermatology 2021.

The sphingosine 1-phosphate (S1P) receptor modulator, etrasimod, recently underwent a phase II clinical trial, with 140 moderate-to-severe atopic dermatitis patients taking 1 mg, 2 mg or placebo orally each day for 12 weeks, said Prof Murrell, Director of Dermatology at the St George Hospital, Sydney.

It found 2 mg etrasimod improved atopic dermatitis symptoms in 29.8% of patients versus 14.9% on 1 mg and 13.0% on placebo (P < 0.05 2 mg versus placebo), when measured using the FDA-preferred validated Investigator Global Assessment tool.

The drug’s impact was less clear using the EASI score, however, with up to 60% of patients in each group (48.4% placebo, 58.7% 1 mg, 57.2% 2 mg etrasimod) seemingly achieving symptom reduction.

“This is a much higher placebo effect than one normally sees in an eczema trial and one has to wonder what was going on there,” Professor Murrell said during the presentation, after leading the study. She wondered whether improper erythema assessment on patients with darker skin, better moisturiser adherence during COVID and less stress could have contributed to the “interesting” result.

Etrasimod patients reported significantly reduced itching in clinic- and home-based questionnaires, particularly within the first five weeks. The home-based responses suggested efficacy tapered during the study’s second half, although they may be influenced by respondent fatigue, said Professor Murrell, who was ICD 2021 Congress President .

“I know from compliance studies that people have responder fatigue if you ask them to repeat doing questions too often and they might just be clicking through to get the job done, without paying attention,” she said.

Meanwhile, etrasimod patients’ quality of life greatly improved versus placebo within two weeks of treatment and was sustained until the end of the trial.

No serious adverse events were observed and nausea, constipation, UTI, back pain, dizziness and headache rates were similar across the treated population and placebo.

As expected, atopic dermatitis flares were more common in the placebo group, she said.

The drug selectively binds S1P receptors 1, 4 and 5, reducing immune cell migration, differentiation and proliferation and improving immune-inflammatory disorders, according to her presentation. It appears to leave receptors 2 and 3 alone, preventing off-target effects such as increased vasoconstriction, fibrosis and proliferation, which may be associated with cardiac, pulmonary and tumour-related risks.

“These encouraging data support the further assessment of etrasimod on itch, quality of life and objective outcome measures in the next phase of clinical development, most likely at 2 mg dose, similar to the ulcerative colitis trials,” she stated.

The full presentation is available via ICD 2021’s website.

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