Astegolimab fails to improve atopic dermatitis outcomes compared with placebo
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Key takeaways:
- Astegolimab binds to ST2 and inhibits IL-33 signaling to reduce inflammation.
- There was a nonsignificant 6.77% difference between the astegolimab and placebo groups regarding changes in Eczema Area and Severity Index scores.
- The astegolimab and placebo groups also did not show any statistically significant differences in secondary outcomes including Investigator Global Assessment scores, pruritus and disease severity.
Although treatment was well tolerated, astegolimab did not effectively improve primary or secondary outcome measurements in atopic dermatitis, according to a study published in The Journal of Allergy and Clinical Immunology.
These results suggest that IL-33/ST2 axis inhibition may not be enough to achieve any treatment benefits for AD, Marcus Maurer, MD, professor of dermatology and allergy and associate director of the Allergie-Centrum-Charité in Berlin, and colleagues wrote in the study.
When the IL-33 cytokine binds to its ST2 receptor, the researchers wrote, inflammatory mediators are released. Astegolimab (Genentech) binds to ST2 and inhibits IL-33 signaling, the researchers continued, which can reduce inflammation mediated by IL-33.
The phase 2, randomized, double-blind, placebo-controlled multicenter study involved patients aged 18 to 75 years with chronic AD assigned to astegolimab (n = 33) or placebo (n = 32).
Patients received 490 mg of astegolimab or placebo on day 1 and at weeks 4, 8 and 12, administered as four subcutaneous abdominal injections, along with a loading dose of 245 mg of astegolimab or placebo via two subcutaneous abdominal injections on day 8.
Between baseline and week 16, patients in the astegolimab group experienced an adjusted mean percent change of –51.47% (95% CI, –68.75 to –34.19) in their Eczema Area and Severity Index (EASI) score, which was the study’s primary outcome, compared with a –58.24% (95% CI, –76.44 to 40.33) change in the placebo group. The difference between the groups was 6.77% (95% CI, –16.57 to 30.11), which the researchers said was not statistically significant.
Also, the researchers found no statistically significant differences between the groups in the study’s secondary outcomes, including changes in Investigator Global Assessment scores, pruritus, body surface area with AD involvement, disease severity, or reductions of 75% or greater from baseline in EASI scores.
When exploratory biomarkers were measured, researchers observed slight reductions in blood eosinophils and serum IL-5 in the astegolimab group at week 16, but they were not statistically different from the placebo group.
The placebo group experienced a trend of decline in median percent change in serum CCL13 levels from baseline to week 16, but the researchers did not observe any similar differences in the astegolimab group.
There were 75 adverse events among 49.2% of the patients, with a higher proportion of patients experiencing at least one adverse event in the placebo group compared with the astegolimab group (58.1% vs. 41.2%). All these events were grade 1 or 2 in severity.
In addition to AD, other common adverse events included nasopharyngitis, conjunctivitis, viral gastroenteritis, abdominal pain and chills.
Overall, the researchers wrote, there were no observable trends for improved or worsened outcomes in any parameter of efficacy with astegolimab treatment even though there was sufficient pharmacokinetic exposure to have produced an effect if one were possible.
Based on these findings, the researchers said that inhibiting the IL-33/ST2 axis is not enough to produce significant treatment benefits for patients with AD.
Perspective
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Astegolimab is a monoclonal antibody targeting IL-33 cytokine signaling by blocking its receptor, ST2, a different target than most of the other treatments approved for atopic dermatitis or currently being studied.
Overall, the results of this study showing no significant effect vs. placebo in patients with AD are not surprising, as a previous treatment targeting the IL-33 cytokine directly also did not show significant results.
There are many exciting treatments that are approved and in the pipeline for AD, but targeting IL-33/ST2 appears to be less promising at this time.
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