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.