Current biologic options for psoriasis include tumor necrosis factor α (TNFα) inhibitors (adalimumab, infliximab, etanercept, certolizumab pegol), IL-17 inhibitors (secukinumab, ixekizumab), IL-12/IL-23 inhibitors (ustekinumab), and IL-23 inhibitors (guselkumab, tildrakizumab, risankizumab).10,11 As patients do not respond uniformly to psoriasis treatment, there has been a drive to develop biologics with novel mechanisms of action that address the needs of patients with inadequate response to first- or second-line biologic therapy.12 Brodalumab, which was approved in 2017 by the US Food and Drug Administration (FDA) for the treatment of adult patients with moderate-to-severe psoriasis who have failed to respond or have lost response to other systemic therapies, blocks the IL-17 receptor (Figure 1).5,13-16
In AMAGINE-1, 42% of patients treated with brodalumab achieved psoriasis area and severity index 100% improvement from baseline (PASI 100) by week 12. Moreover, the PASI 100 response rate was 74% at week 52, which was maintained through week 120.17 Similarly, in AMAGINE-2, patients treated with continuous brodalumab achieved a PASI 100 rate of 65% at week 52, which remained stable through week 120 at 61%.18 Meta-analyses also support this evidence, indicating that brodalumab has greater long-term PASI response rates compared with ustekinumab and adalimumab.10
The long-term efficacy and rapid onset of treatment effect seen in brodalumab clinical trials (AMAGINE-1/-2/-3) is likely to be in part attributable to its unique mechanism.2,19 By targeting the IL- 17 receptor, brodalumab influences the activity of multiple IL-17 isoforms (IL-17A, IL-17A/F, IL-17C, IL-17E, and IL-17F),16 which may contribute to its efficacy. In contrast, other IL-17–directed drugs target only a subset of isoforms; secukinumab and ixekizumab are IL-17A inhibitors, whereas the currently investigational drug bimekizumab only targets IL-17A and IL-17F.8,20
The immunogenicity profile of brodalumab also supports its potential efficacy as a long-term treatment option. In a longterm analysis of 4246 patients treated with brodalumab in phase 2 and 3 trials, only 2% developed brodalumab-specific antibodies, and in more than half of these patients (1%), these antibodies were transient.3 In contrast, analyses of adalimumab have shown that antidrug antibodies may occur in 17% to 45% of patients treated for 24 weeks.21 Among 1079 evaluable patients who received risankizumab for psoriasis treatment, incidences of antidrug antibodies and neutralizing antibodies were 24% and 14%, respectively, over 52 treatment weeks.22 Moreover, 7% of patients treated with guselkumab for 48 weeks and 7% of patients treated with tildrakizumab for up to 64 weeks developed antidrug antibodies.3 Because antidrug antibodies are one of the mechanisms that contribute to loss of biologic effect over time, the results of brodalumab compare favorably to other biologic drugs and may in part account for its durable efficacy.21
Brodalumab was approved by the US FDA after evidence for its use as a long-term, effective therapy for patients with prior biologic failure. Most of these data come from the aforementioned pivotal phase 3 AMAGINE trials, which compared brodalumab with placebo (AMAGINE-1) and ustekinumab (AMAGINE-2/-3). In these trials, prior biologic exposure and prior biologic failure were assessed at baseline.2,19 During the 12-week induction period of AMAGINE-2/-3, 1236 patients received brodalumab 210
