التفاصيل البيبلوغرافية
| العنوان: |
Biological impact of iberdomide in patients with active systemic lupus erythematosus. |
| المؤلفون: |
Lipsky, Peter E., van Vollenhoven, Ronald, Dörner, Thomas, Werth, Victoria P., Merrill, Joan T., Furie, Richard, Petronijevic, Milan, Velasco Zamora, Benito, Majdan, Maria, Irazoque-Palazuelos, Fedra, Terbrueggen, Robert, Delev, Nikolay, Weiswasser, Michael, Korish, Shimon, Stern, Mark, Hersey, Sarah, Ying Ye, Gaudy, Allison, Zhaohui Liu, Gagnon, Robert |
| المصدر: |
Annals of the Rheumatic Diseases; Aug2022, Vol. 81 Issue 8, p1136-1142, 7p |
| مستخلص: |
Objectives: Iberdomide is a high-affinity cereblon ligand that promotes proteasomal degradation of transcription factors Ikaros (IKZF1) and Aiolos (IKZF3). Pharmacodynamics and pharmacokinetics of oral iberdomide were evaluated in a phase 2b study of patients with active systemic lupus erythematosus (SLE).Methods: Adults with autoantibody-positive SLE were randomised to placebo (n=83) or once daily iberdomide 0.15 mg (n=42), 0.3 mg (n=82) or 0.45 mg (n=81). Pharmacodynamic changes in whole blood leucocytes were measured by flow cytometry, regulatory T cells (Tregs) by epigenetic assay, plasma cytokines by ultrasensitive cytokine assay and gene expression by Modular Immune Profiling.Results: Iberdomide exhibited linear pharmacokinetics and dose-dependently modulated leucocytes and cytokines. Compared with placebo at week 24, iberdomide 0.45 mg significantly (p<0.001) reduced B cells, including those expressing CD268 (TNFRSF13C) (-58.3%), and plasmacytoid dendritic cells (-73.9%), and increased Tregs (+104.9%) and interleukin 2 (IL-2) (+144.1%). Clinical efficacy was previously reported in patients with high IKZF3 expression and high type I interferon (IFN) signature at baseline and confirmed here in those with an especially high IFN signature. Iberdomide decreased the type I IFN gene signature only in patients with high expression at baseline (-81.5%; p<0.001) but decreased other gene signatures in all patients.Conclusion: Iberdomide significantly reduced activity of type I IFN and B cell pathways, and increased IL-2 and Tregs, suggesting a selective rebalancing of immune abnormalities in SLE. Clinical efficacy corresponded to reduction of the type I IFN gene signature.Trial Registration Number: NCT03161483. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
