In a two-stage phase II dose-ranging trial, once-monthly treatment with tilrekimig yields high clinical response rates and reduces itching in biologic-naïve adults with mild-to-moderate atopic dermatitis (AD).
The study met its primary endpoint across all doses, with all evaluated doses showing a statistically significant increase in the proportion of participants achieving EASI-75* at week 16 vs placebo.
In stage 1 of the trial, up to 62.5 percent of patients treated with tilrekimig achieved EASI-75 compared with 19.9 percent of those who received placebo (p=0.0008). In stage 2, 47.8 to 61 percent of those treated with tilrekimig achieved EASI-75 vs 9.1 percent of those who received placebo (p<0.003).
Unlike single cytokine-targeting therapies that block interleukin (IL)-4 and IL-13, tilrekimig binds to and inhibits three distinct inflammatory pathways in AD: IL-4, IL-13, and thymic stromal lymphopoietin (TSLP).
“I think this is the first time we’ve seen public data on a trispecific for AD,” said study author Dr Eric Simpson of the Department of Dermatology at Oregon Health & Science University in Portland, Oregon, US, at EADV 2026.
vIGA-AD response
The trial enrolled biologic-naive adults with moderate-to-severe AD and a baseline EASI score of ≥16. In stage 1, patients received subcutaneous tilrekimig 450 mg (n=41) or placebo (n=20) every 2 weeks. In stage 2, patients received tilrekimig 400 mg (n=41), 200 mg (n=41), 50 mg (n=23), or placebo (n=22) every 4 weeks up to week 16. [EADV 2026, abstract AS-1730]
Secondary endpoints included the proportion of patients with clear or almost clear skin, defined as a vIGA-AD** score of 0/1 with at least a 2-point improvement from baseline at week 16, the proportion who achieved an EASI-75 response over time, and safety outcomes.
In stage 1, 30.3 percent of patients receiving tilrekimig and 11.8 percent of those on placebo achieved vIGA-AD 0/1 (p=0.0251). Across the stage 2 dose groups, 26–27 percent of patients achieved vIGA-AD 0/1 vs zero percent with placebo (p<0.006 for all). Just over one quarter of tilrekimig-treated patients achieved this endpoint, regardless of dose.
Simpson acknowledged that vIGA response rates were well below EASI-75 results at every dose. He said clinicians should focus on the placebo-adjusted effect size, noting that the placebo-adjusted vIGA difference was not necessarily greater than that of currently available biologics, although trial populations differ. Whether additional dosing could widen the difference remains unclear.
In an exploratory analysis, 43 percent and 51 percent of patients receiving the 400 mg and 200 mg monthly doses achieved ≥ a 4-point reduction in the weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) score vs only 7 percent with placebo. Significant improvement was not observed with the 50 mg dose or placebo (8.2 percent and 7.2 percent, respectively).
A positive sign
Tilrekimig was well tolerated, with no dose-dependent safety signals and an adverse event rate comparable to placebo. No conjunctivitis signal emerged through 16 weeks. “The fact that there was no conjunctivitis at Q4 week dosing is a positive sign; that’s new for the class,” said Simpson. He added that if larger trials confirm this finding, it could suggest that TSLP blockade offers a protective effect.