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The oral S1P receptor modulator has promise to break new ground for disease modification.
Etrasimod, an oral selective sphingosine 1-phosphate (S1P) receptor modulator, offers promise as a new therapeutic option for atopic dermatitis, according to a late-breaking study presented at the American Academy of Dermatology (AAD) Virtual Meeting Experience 2021.
The phase 2 ADVISE trial results showed that treated patients achieved significant improvements in patient- and clinician-based assessments after 12 weeks.
The study was led by Emma Guttman-Yassky, MD, PhD, Professor and System Chair of Dermatology, Icahn School of Medicine at Mount Sinai, and was the first the assess S1P modulation as a potential new mechanism of treatment for patients with moderate-to-severe atopic dermatitis.
“The idea behind this novel mechanism is that you prevent immune cells, or lymphocytes, from going to the skin,” Guttman-Yassky explained in an interview with HCPLive®. “By [doing this], you basically improve disease. But maybe—and this is my wishful thinking […]—we’ll prevent new lesions in the future.”
The investigators thus enrolled 140 participants across 3 countries—the United States, Canada, and Australia. A majority of the population (61.4%) was female.
All enrollees were age 18-70 years and reported Eczema Area and Severity Index (EASI) ≥ 16, validated Investigator Global Assessment (vIGA) ≥3, and Body Surface Area ≥10% at baseline.
They were then randomized 1:1:1 to receive etrasimod 1 mg, etrasimod 2 mg, and placebo for 12 weeks, with a 4-week follow-up period.
The primary endpoint sought by Guttman-Yassky and her team was the percent change in EASI from baseline to week 12. A key secondary endpoint included the proportion of patients with vIGA 0 or 1 in addition to a reduction from baseline of ≥2 points at the end of the treatment period.
Furthermore, measured patient-reported outcomes were the percent change in weekly peak pruritis NRS at week 12, change in dermatology life quality index (DLQI), and change in patient-oriented eczema measure (POEM).
So far, the investigators have reported on the secondary and patient-reported outcomes. As such, 29.8% of patients who received etrasimod 2 mg achieved vIGA 0 or 1 at week 12—compared with 14.9% for etrasimod 1 mg and 13.0% for placebo (versus 2 mg: P<.05).
Additionally, 42.1% in the etrasimod 2 mg group achieved improvements of ≥4 points in peak pruritis NRS, as did 32.5% and 27.0% in the 1 mg and placebo groups, respectively (P<.05).
Similar patterns were noted for DLQI and POEM, which saw more patients on etrasimod achieve ≥4-point improvements compared to placebo.
For DLQI, such improvements were reported in 85.7% on etrasimod 2 mg, 82.9% on etrasimod 1 mg, and 64.1% on placebo (versus 2 mg: P<.05).
However, for POEM, improvements were reported in 73% on 2 mg, 80.6% on 1 mg, and 43.6% on placebo (versus 2 mg: P < .05; versus 1 mg: P <.01).
Overall, treatment was considered well-tolerated and consistent with previous findings, with up to 59.6% of patients who took etrasimod 2 mg experiencing treat-emergent adverse events. The most common events were nausea (6.4%), constipation (6.4%), urinary tract infection (6.4%), back pain (6.4%), dizziness (6.4%), and atopic dermatitis (4.3%). No serious adverse events were reported across the 3 treatment arms.
Nonetheless, Guttman-Yassky expressed hope that longer-term data will truly demonstrate the drug’s potential.
“With such a mechanism, we treat the disease a little bit indirectly,” she noted. “Even though we have significance in this study, I think data will be even better for longer-term duration.”
Watch the interview below: