Spotlight on brodalumab in the treatment of moderate-to-severe plaque psoriasis: design, development, and potential place in therapy

Abstract

Brodalumab is a novel fully human immunoglobulin G2 monoclonal antibody that antagonizes the interleukin (IL)-17 pathway by binding with high affinity to human IL-17RA. The role of IL-17A in the pathogenesis of psoriasis, as well as the remarkable effectiveness of IL-17 inhibitors in the treatment of moderate-to-severe plaque psoriasis, is well established. The mechanism of action of brodalumab is unique in that it inhibits the IL-17 receptor compared to the two other currently FDA-approved IL-17 inhibitors, secukinumab and ixekizumab, which inhibit the IL-17A molecule itself. The efficacy of brodalumab in the treatment of moderate-to-severe plaque psoriasis has been demonstrated in phase 2 and 3 trials, and subsequently the FDA approved this medication in February 2017. Brodalumab was approved in Japan in July 2016 and approval is pending in Europe. The safety and adverse effects of brodalumab were reviewed across several clinical trials, which, similar to other IL-17 inhibitors, demonstrated increased rates of neutropenia and Candida infections. Brodalumab treatment, similar to ixekizumab and secukinumab, showed no improvement in inflammatory bowel disease patients, and on the contrary, more exacerbations were encountered. Suicidal ideation and behavior events have been reported with brodalumab treatment and are of significant concern. Brodalumab provides another highly effective treatment option for moderate-to-severe plaque psoriasis.

Comparable efficacy and safety of brodalumab in obese and nonobese patients with psoriasis: analysis of two randomized controlled trials

“…Brodalumab, a biologic therapy that disrupts pathogenic cytokine signalling associated with psoriasis by binding to IL‐17RA, inhibits signalling of IL‐17 family members, including IL‐17A, IL‐17E and IL‐17F . It is administered at the same dose (210 mg Q2W) for all patients regardless of body weight.…”

“…Brodalumab, a biologic therapy that disrupts pathogenic cytokine signalling associated with psoriasis by binding to IL-17RA, inhibits signalling of IL-17 family members, including IL-17A, IL-17E and IL-17F. 15 It is administered at the same dose (210 mg Q2W) for all patients regardless of body weight. Other biologic therapies for psoriasis, some of which use weight-based dosing, have been shown to be less efficacious in heavier or obese vs. lighter or nonobese patients.…”

<p>Brodalumab for the treatment of moderate-to-severe psoriasis: case series and literature review</p>

“…There are five IL-17 cell surface receptors: RA to RE. IL-17RA forms heterodimers with each of IL-17RC, IL-17RB and IL-17RE 6,8. The complexity of the etiology explains the diversity of symptoms and variable influence of environmental factors in psoriatic disease 2…”

“…Blocking IL-17RA inhibits IL-17 cytokine-induced responses resulting in normalization of inflammation in the skin 12. This mechanism is different from that of other available biologics targeting the Th-17 axis (eg, secukinumab and ixekizumab each bind selectively to IL-17A) 5,8…”

Malignancy Rates in Brodalumab Clinical Studies for Psoriasis

“…Across three large phase III studies of brodalumab for the treatment of moderate-to-severe plaque psoriasis, 75% improvement in psoriasis area severity index (PASI 75) response rates ranged from 83% to 86% in patients receiving brodalumab 210 mg every 2 weeks (Q2W) compared with 3% to 8% in those receiving placebo [10,11]. Brodalumab is a targeted immunomodulatory agent and is not expected to be broadly immunosuppressive [12,13]. A network meta-analysis of 109 studies of treatments for chronic plaque psoriasis (which included three studies of brodalumab versus placebo and two studies of brodalumab versus the active comparator ustekinumab and placebo) did not find evidence of increased risk of serious adverse events (AEs) with brodalumab [14].…”