Efficacy of Brodalumab in Patients with Psoriasis and Risk Factors for Treatment Failure: A Review of Post Hoc Analyses

Abstract

Factors such as obesity, alcohol consumption, and tobacco use are associated with both increased psoriasis severity and inadequate response to systemic and biologic therapies. Obesity is linked to chronic inflammation, which can contribute to psoriasis pathogenesis. Fixed-dose therapies may have reduced efficacy in patients with a higher body mass index, while weight-based dosing can increase the burden of drug-specific side effects. Alcohol and nicotine from tobacco have also been shown to stimulate keratinocyte and immune cell proliferation and production of proinflammatory cytokines. While these risk factors are prevalent among patients with moderate-to-severe psoriasis, their influence on treatment outcomes may be overlooked when evaluating therapeutic options. Brodalumab is a fully human interleukin-17 receptor A antagonist approved for the treatment of moderate-to-severe psoriasis. In this review, we describe the lifestyle-related risk factors associated with decreased response to treatment. We further summarize the post hoc analyses of brodalumab in participant subgroups with moderate-to-severe psoriasis and a history of prior biologic failure, obesity, and alcohol or tobacco use from two phase 3 clinical trials (AMAGINE-2 and AMAGINE-3; ClinicalTrials.gov identifiers: NCT01708603 and NCT01708629, respectively). Our review of clinical trial and real-world data suggests that brodalumab is an efficacious and safe treatment option for patients with lifestyle factors that increase the likelihood of treatment failure, allowing them to achieve skin clearance and improve quality of life.

Keywords: Alcohol; Biologic therapy; IL-17 receptor A inhibitor; Obesity; Plaque psoriasis; Tobacco.

Fig. 1

Mechanism of action of brodalumab. The IL-17A, IL-17C, IL-17F, and IL-17E isoforms are overexpressed in psoriatic skin, with the protein level of IL-17C being the highest among IL-17 family members within lesions [43, 44]. IL-17 is produced by various cells, including T_H17 cells (primed by dendritic cells) that express IL-17A and IL-17F as well as keratinocytes that produce IL-17C and IL-17E in an autocrine manner [44, 45]. IL-17 isoforms activate specific IL-17 receptors to induce inflammation, angiogenesis, and keratinocyte proliferation [45, 46]. Brodalumab blocks signaling induced by IL-17A, IL-17F, IL-17C, and IL-17E [20], whereas anti–IL-17 antibodies selectively bind IL-17A (secukinumab and ixekizumab) or IL-17A and IL-17F (bimekizumab) [–49]. CCL20, chemokine (C–C motif) ligand 20; G-CSF, granulocyte colony stimulating factor; IL, interleukin; IL-17R, IL-17 receptor; TGF-β, transforming growth factor-β; T_H, T helper cell

Fig. 2

PASI scores in participants rescued with brodalumab [50]. a Percentage of participants with PASI 75, PASI 90, and PASI 100 in the brodalumab rescue group compared with the continued ustekinumab group at week 52. b PASI response rates at weeks 12 and 52 in participants rescued with brodalumab after inadequate response to ustekinumab at week 16. PASI, Psoriasis Area and Severity Index. This original figure reports select data points published in Langley RG, Armstrong AW, Lebwohl MG, et al. Efficacy and safety of brodalumab in participants with psoriasis who had inadequate responses to ustekinumab: subgroup analysis of two randomized phase III trials. Br J Dermatol. 2019;180(2):306–314

Fig. 3

Representative images from a participant with obesity treated with brodalumab in a long-term extension of a phase 2 study (NCT00975637) [59]. Images were provided with participant consent

Fig. 4

Measures of skin clearance at week 12 and week 52 stratified by biologic treatment and BMI category [21]. a Percentage of participants achieving PASI 75, 90, and 100 with continuous brodalumab by obesity status. b Percentage of participants achieving PASI 75, 90, and 100 in participants with obesity receiving continuous ustekinumab or brodalumab or those who were rescued with brodalumab after failing to respond to ustekinumab. The continuous brodalumab treatment group includes participants who received brodalumab 210 mg Q2W throughout the study. The continuous ustekinumab treatment group includes participants who received ustekinumab throughout the study. The brodalumab rescue group includes participants who initially received ustekinumab and were rescued at week 16 with brodalumab 210 mg Q2W. BMI, body mass index; PASI, Psoriasis Area and Severity Index; Q2W, every 2 weeks (Q2W). This original figure reports select data points published in Hsu S, Green LJ, Lebwohl MG, Wu JJ, Blauvelt A, Jacobson AA. Comparable efficacy and safety of brodalumab in obese and nonobese patients with psoriasis: analysis of two randomized controlled trials. Br J Dermatol. 2020;182(4):880–888