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Войти в исследования The Journal of allergy and clinical immunology · 2026
Bimekizumab long-term response in psoriasis: Mechanistic insights into efficacy level and durability.
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Krueger James G, Cutcutache Ioana, Lebwohl Mark, Gudjonsson Johann E, Pinter Andreas, Langley Richard G, Merola Joseph, Tada Yayoi, Skelton Andrew, Rastrick Joe, Ferecskó Alex S, Page Matthew, Davies Owen, López Pinto José Manuel, Warham Rhys, Shaw Stevan, Warren Richard B
Аннотация
BACKGROUND: Bimekizumab (BKZ), an IL-17A and IL-17F inhibitor, has demonstrated a rapid and high level of complete skin clearance in patients with psoriasis and complete normalization of the transcriptional signature of lesional skin after 8 weeks.
OBJECTIVE: We sought to assess the durability of initial clinical response to BKZ for up to 4 years and investigate molecular mechanisms leading to the observed response.
METHODS: Clinical data were pooled from 3 1-year phase 3 feeder studies (BE VIVID, BE READY, and BE SURE) and their 3-year open-label extension (BE BRIGHT). Transcriptomic analyses were conducted on 3 independent single-cell RNA-sequencing data sets from lesional psoriasis biopsies and bulk RNA-sequencing data from a phase 2a study.
RESULTS: Among patients who achieved complete skin clearance after 16 weeks, continued to receive double-blind BKZ treatment, and entered BE BRIGHT, 73.0% achieved this response at the end of year 4 (N = 503; modified nonresponder imputation). Single-cell transcriptomic analyses revealed a group of tissue-resident memory T (TRM) cells in lesional skin expressing IL17A and/or IL17F that are minimally present in healthy skin, postulated to constitute a pathogenic TRM-cell subset. Prosurvival factors expressed in TRM cells in lesional skin were identified, with IL7R shown to be more highly expressed in IL17F+ than in IL17A+ TRM cells. Reversal of expression of these prosurvival factors, alongside a general TRM gene signature, was demonstrated in bulk transcriptomic analyses after 8 weeks of treatment (2 BKZ doses).
CONCLUSIONS: The strong durability and high response level observed with BKZ may be associated with normalization of pathogenic TRM cells.
OBJECTIVE: We sought to assess the durability of initial clinical response to BKZ for up to 4 years and investigate molecular mechanisms leading to the observed response.
METHODS: Clinical data were pooled from 3 1-year phase 3 feeder studies (BE VIVID, BE READY, and BE SURE) and their 3-year open-label extension (BE BRIGHT). Transcriptomic analyses were conducted on 3 independent single-cell RNA-sequencing data sets from lesional psoriasis biopsies and bulk RNA-sequencing data from a phase 2a study.
RESULTS: Among patients who achieved complete skin clearance after 16 weeks, continued to receive double-blind BKZ treatment, and entered BE BRIGHT, 73.0% achieved this response at the end of year 4 (N = 503; modified nonresponder imputation). Single-cell transcriptomic analyses revealed a group of tissue-resident memory T (TRM) cells in lesional skin expressing IL17A and/or IL17F that are minimally present in healthy skin, postulated to constitute a pathogenic TRM-cell subset. Prosurvival factors expressed in TRM cells in lesional skin were identified, with IL7R shown to be more highly expressed in IL17F+ than in IL17A+ TRM cells. Reversal of expression of these prosurvival factors, alongside a general TRM gene signature, was demonstrated in bulk transcriptomic analyses after 8 weeks of treatment (2 BKZ doses).
CONCLUSIONS: The strong durability and high response level observed with BKZ may be associated with normalization of pathogenic TRM cells.