Narrative Review of the Emerging Therapeutic Role of Brodalumab in Difficult-to-Treat Psoriasis

Abstract

Psoriatic involvement in areas of the body such as nails, palms and soles (palmoplantar), and scalp is associated with dramatically negative effects on quality of life relative to involvement elsewhere in the body. Although numerous evidence-based studies demonstrate the efficacy of biologics for overall skin clearance in moderate-to-severe plaque psoriasis (including tumor necrosis factor α [TNFα] inhibitors and interleukin [IL]-17A, IL-12/IL-23, IL-23, IL-17F, and IL-17A/F inhibitors), large, randomized, placebo-controlled clinical studies of psoriasis with nail, palmoplantar, and scalp involvement are needed to better inform decision-making in clinical practice. Moreover, biologic failure caused by drug ineffectiveness is a common occurrence in patients who do not respond, lose response, or are intolerant to treatment. Brodalumab is a fully human IL-17 receptor A antagonist that demonstrates high rates of skin clearance among the latest generation of biologic therapies for treatment of moderate-to-severe psoriasis. This review summarizes current literature on the efficacy of brodalumab and other therapies in difficult-to-treat psoriasis including psoriasis in difficult-to-treat locations (such as psoriasis with nail, palmoplantar, or scalp involvement) and psoriasis in patients whose disease did not respond to other biologics.

Keywords: Biologic therapy; IL-17 receptor A inhibitor; IL-17A inhibitor; Nail psoriasis; Nail psoriasis severity index; Palmoplantar psoriasis; Palmoplantar psoriasis and severity index; Psoriasis scalp severity index; Scalp psoriasis.

Fig. 1

Mechanism of action of brodalumab. Inflammatory response in psoriasis is mediated by T_H17 and several other IL-17–producing cells. These ligands bind to the IL-17R complex, which is composed of IL-17RA and IL-17RC chains. IL-17R is expressed on various target cells in psoriatic lesions, including endothelial cells, keratinocytes, dendritic cells, and macrophages. Anti-IL-17A antibodies, such as secukinumab and ixekizumab, selectively target IL-17A but not the other isoforms; bimekizumab targets IL-17A, IL-17F, and IL-17A/F. In contrast, brodalumab blocks the IL-17RA subunit, thereby inhibiting the signaling of multiple inflammatory cytokines involved in psoriasis, including IL-17A, IL-17C, IL-17E, IL-17F, and IL-17A/F. Eventually, several downstream inflammatory factors that target gene expression are inhibited [22, 25, 26]. IL interleukin, IL-17R IL-17 receptor, IL-17RA IL-17 receptor A, IL-17RC IL-17 receptor C, T_H17 helper T cell (subtype 17)

Fig. 2

Percentage of patients in the AMAGINE-2/-3 trials with NAPSI 0 at weeks 12, 36, and 52 receiving either continuous brodalumab 210 mg Q2W or continuous ustekinumab [36]. Observed data analysis. Error bars are 95% CI. N1 number of patients who had a valid measurement value at the specified week, NAPSI nail psoriasis severity index, Q2W every 2 weeks. *P < 0.05 versus ustekinumab

Fig. 3

Mean NAPSI of fingers and toes at baseline and weeks 12 and 24 after treatment with brodalumab (N = 30) in an open-label, unblinded study [37]. Error bars are SD. NAPSI nail psoriasis severity index. *P < 0.001 versus baseline

Fig. 4

Proportion of PASI 75, PASI 90, and PASI 100 responders at week 16 after rescue with brodalumab (a) in a study of 47 individuals who switched treatment from secukinumab, ixekizumab, or both [55] and (b) in a separate study of 39 patients who failed treatment with secukinumab or ixekizumab [56]. PASI 75, 90, and 100 psoriasis area and severity index 75%, 90%, and 100% improvement