Effectiveness of brodalumab after previous treatment failure of interleukin‐17A inhibitors in patients with psoriasis

Abstract

Studies on switch between interleukin (IL)-17 inhibitors are scarce. We assessed the effectiveness of brodalumab in patients with previous treatment failure of . Patients with psoriasis and previous treatment failure of an IL-17A inhibitor were treated with brodalumab at standard dose. Effectiveness was assessed after 12, 26, and 52 weeks of treatment. The primary outcome was the proportion of patients that had achieved an absolute psoriasis area and severity index (PASI) ≤2 and/or a relative reduction of PASI of 75% (PASI75) at week 12. Plasma cytokine levels were measured at baseline and after 12 weeks of treatment. In total, 20 patients were included, seven (35%) were female, the median age was 50 years, and the median baseline PASI was 13.5. Analyzing the data using nonresponder imputation, 14 (70%) patients had achieved either PASI75 and/or PASI ≤2, 8 (40%) had achieved PASI90, and three (15%) had achieved PASI100 at week 12. In total, nine patients (45%) completed the 52-weeks trial and seven patients (35%) still had PASI75 throughout 52 weeks. Seventeen out of 20 patients experienced any adverse events (AEs) during 52 weeks with no serious AEs or deaths. Patients responding to treatment had lower levels of tumor necrosis factor (TNF)-α and IL-6 at baseline compared with those who did not respond to treatment (TNF-α, p = 0.041, IL-6, p = 0.0054). In conclusion, treatment with brodalumab despite previous treatment failure with an IL-17A inhibitor can be effective and well-tolerated.

Brodalumab in plaque psoriasis: Real‐world data on effectiveness, safety and clinical predictive factors of initial response and drug survival over a period of 104 weeks

“…Overall, any previous exposure to IL‐17 inhibitors should not discourage the clinician to initiate brodalumab treatment. The positive effect of early response in drug survival has also been highlighted in other studies 19‐28 …”

Circulating Brodalumab Levels and Therapy Outcomes in Patients With Psoriasis Treated With Brodalumab

“…In this case series, we monitored the levels of brodalumab and antibrodalumab antibodies in 20 patients with psoriasis treated with brodalumab whose prior treatment failed with at least one IL-17A inhibitor and in most cases also failed with several other antibody-based therapies, including anti–IL-12/23, anti–IL23, and TNF-α inhibitors (eTable in the Supplement). As reported previously, the study did not include placebo controls for comparison but 14 of the 20 participants (70%) were PASI 75 responders after 12 weeks of therapy and 7 of the 20 participants (35%) were PASI 75 responders after 52 weeks of therapy, suggesting that brodalumab may have utility in these otherwise treatment-refractory patients.…”

“…As described previously, the study was conducted in accordance with the Declaration of Helsinki and approved by the local ethics committee, the data protection agency, and the Danish Medicines Agency. Written informed consent was obtained from all patients prior to inclusion.…”

“…As described previously, plasma levels of IL-17A, IL-17F, IL-23, IL-6, interferon (IFN)-γ, and TNF-α were measured using a custom multiplex Luminex High-Performance Assay (Bio-techne Ltd), as instructed by the vendor. The stated sensitivities were 2.5 pg/mL for IL-17A, 9.2 pg/mL for IL-17F, 20.2 pg/mL for IL-23, 0.7 pg/mL for IL-6 1.9 pg/mL for IFN-γ, and 1.1 pg/mL for TNF-α.…”

Real‐life intraclass switch among IL‐17 inhibitors in psoriasis: results from a single‐centre, 24‐week, retrospective study

“…Our results corroborate previous studies implying that loss of response or no response to a first anti-IL17 agent does not prejudge failure to a second anti-IL-17 inhibitor. [2][3][4][5][6][7][8][9][10] Nevertheless, larger, long-term studies are needed to draw definitive conclusions.…”