mg every 2 weeks. Of those patients, 27% (n=334) had exposure to at least one prior biologic, with most having been treated with TNFα inhibitors (89% [n=296]).5 Furthermore, in AMAGINE-2/-3, a subset of the ustekinumab-treated patients who had inadequate treatment response switched to brodalumab so that the efficacy of brodalumab as a rescue therapy could be assessed.23
Because up to 60% of patients report prior biologic exposure in other clinical trials of biologics for psoriasis, understanding how prior exposure correlates with treatment effect is highly relevant.4 Patients with prior biologic exposure are likely to have more severe psoriasis that requires a longer treatment duration, and it is therefore important that they switch to a biologic agent with long-term effectiveness.4 Herein, we highlight the evidence for the long-term improvement of psoriasis after brodalumab treatment in patients with inadequate response to prior biologics. These data may help inform clinical decisions when a change in therapy is required to achieve long-term skin clearance.
Brodalumab Improves Plaque Psoriasis Lesions After Failure of IL-17 Inhibitors
Brodalumab is a viable treatment option for patients who fail to respond to other IL-17 inhibitors.5 In a retrospective study of patients switching to brodalumab after secukinumab or ixekizumab failure, 50% (3/7) and 67% (2/3) achieved PASI 75, respectively, after 12 weeks of treatment.24,25 Similarly, in an open-label study measuring outcomes for 39 patients switching to brodalumab after being treated with secukinumab or ixekizumab for ≥3 months without achieving PASI 75 or with a 50% loss of original improvement, 76%, 50%, and 32% achieved PASI 75, PASI 90, and PASI 100, respectively, after 16 weeks of brodalumab treatment.24,26 In another cohort of 23 patients with prior IL-17A-inhibitor failure, 48% achieved PASI 75 after 12 weeks of brodalumab treatment.24 In 16 patients with psoriasis who were treated with brodalumab after failing secukinumab treatment, 75% achieved PASI 100 at week 16.27
One study of 20 patients with IL-17A-inhibitor treatment failure found that brodalumab improved outcomes at 3 months with no significant difference between patients with primary treatment failure and secondary treatment failure (PASI 75, PASI ≤2, or both achieved in 67% [2/3] and 71% [12/17] of patients with primary or secondary treatment failure, respectively). Overall, PASI 90 and PASI 100 were achieved in 40% and 15% of patients, respectively. Additionally, half of patients achieved dermatology life quality index of 0 or 1 after 3 months of brodalumab treatment.28 Although these study populations are relatively small, they indicate that a substantial proportion of individuals can achieve improvement in psoriasis with brodalumab after IL-17-inhibitor treatment. By binding to the IL-17 receptor, brodalumab not only acts upon a distinct part of the pathogenic pathway in psoriasis, but it may have broader effects compared with biologics that only inhibit limited IL-17 isoforms.8
The switch from IL-17 inhibitors to brodalumab after inadequate treatment response is supported by real-world evidence. For example, in a retrospective study of 47 patients with plaque psoriasis who initiated brodalumab after secukinumab or ixekizumab treatment (or both), most (94%) switched treatments specifically because of nonresponse. Of those, 30% discontinued secukinumab, 28% discontinued ixekizumab, and 43% discontinued previous treatment with both drugs. At week 16, 62%, 47%, and 43% of patients achieved PASI 75, PASI 90, and PASI 100, respectively (Figure 2).24 Response to brodalumab, measured by PASI 90, was seen across subgroups stratified by a number of previous biologics. For those with one prior biologic treatment, the rate of PASI 90 success with
