Key messages
- Bimekizumab è un anticorpo monoclonale che inibisce selettivamente sia l’interleuchina (IL)-17A che l’IL-17F, attualmente in fase di sperimentazione per il trattamento della psoriasi moderata-severa.
- Nel presente studio l’inibizione dell’IL-17F oltre a quella dell’IL-17A ha determinato rapide ed elevate risposte cliniche. Inoltre, è stata osservata una significativa normalizzazione della biologia dei cheratinociti e del transcriptoma psoriasico, tra cui la normalizzazione dell’espressione dei geni dell’IL-17 e dell’IL-23 entro l’8va settimana.
- Tali dati forniscono evidenze per supportare la valutazione del dosaggio di mantenimento di bimekizumab sia ogni 8 che ogni 4 settimane nei trial clinici di fase III.
Abstract
Background
Bimekizumab is a monoclonal antibody that selectively inhibits both interleukin (IL)-17A and IL-17F, which is currently under investigation for treatment of moderate-to-severe plaque psoriasis. Maintenance dosing every 4 weeks is well established with IL-17 inhibitors for psoriasis.
Objectives
To investigate the possible dosing interval during bimekizumab maintenance therapy to maintain clear skin, to inform phase III studies.
Methods
Forty-nine patients with moderate-to-severe plaque psoriasis received bimekizumab 320 mg at weeks 0/4, followed at week 16 by bimekizumab 320 mg (n = 17) or placebo (n = 32). Efficacy, safety, pharmacokinetics, immunogenicity and biopsy transcriptomic analyses were assessed to week 28.
Results
At week 8, 47% of patients achieved a 100% improvement from baseline in Psoriasis Area and Severity Index (PASI 100), increasing to 57% at week 12 (8 weeks after the second dose) before decreasing. In those who received bimekizumab at week 16, PASI 100 rate increased to comparable peak levels at week 20, but reduced by week 28 to 41% (12 weeks after the third dose). The week 8 transcriptional signature observed in lesional psoriatic skin rapidly normalized to levels consistent with nonlesional skin, resulting in molecular remission. Keratinocyte-related gene products such as CXCL1 (C-X-C motif chemokine ligand 1), IL-8 (encoded by the CXCL8 gene), CCL20 (C-C motif chemokine 20), IL-36γ and IL-17C were profoundly normalized to levels associated with nonlesional skin.
Conclusions
Here, inhibition of IL-17F in addition to IL-17A resulted in rapid, deep clinical responses. Additionally, profound normalization of keratinocyte biology and the psoriatic transcriptome was observed, including normalization of both IL17 and IL23 gene expression by week 8. These data provide evidence to support evaluation of bimekizumab maintenance dosing both every 8 and every 4 weeks in phase III clinical trials.