A phase 4, randomized, head‐to‐head trial comparing the efficacy of subcutaneous injections of brodalumab to oral administrations of fumaric acid esters in adults with moderate‐to‐severe plaque psoriasis (CHANGE)

Abstract

Background Brodalumab is a fully human monoclonal immunoglobulin IgG2 antibody that binds to the human IL‐17 receptor subunit A and by that inhibits the biologic action of IL‐17A, IL‐17F, IL‐17C and IL‐17E. Therapy with fumaric acid esters (FAE) is a well established and widely used first‐line systemic treatment for subjects with moderate‐to‐severe plaque psoriasis. Objectives To compare brodalumab to FAE in terms of clinical efficacy, patient‐reported outcomes and safety in subjects with moderate‐to‐severe plaque psoriasis who were naïve to systemic treatment. Methods Eligible subjects were randomized 1 : 1 to 210 mg brodalumab injections or oral FAE according to product label in this 24‐week, open‐label, assessor‐blinded, multi‐centre, head‐to‐head phase 4 trial. The primary endpoints were having PASI75 and having sPGA score of 0 or 1 (sPGA 0/1). Subjects with missing values for the primary endpoints were considered non‐responders. Results A total of 210 subjects were randomized. 91/105 subjects completed brodalumab treatment and 58/105 subjects completed FAE treatment. At Week 24, significantly more subjects in the brodalumab group compared to the FAE group had PASI75 (81.0% vs. 38.1%, P < 0.001) and sPGA 0/1 (64.8% vs. 20.0%, P < 0.001). In the brodalumab group, the median time to both PASI75 and to PASI90 was significantly shorter than in the FAE group (4.1 weeks vs. 16.4 weeks, and 7.4 weeks vs. 24.4 weeks, respectively, P < 0.0001 for both). The rate of adverse events was lower in subjects treated with brodalumab compared to subjects treated with FAE (616.4 vs. 1195.8 events per 100 exposure years). No new safety signals were detected for brodalumab. Conclusions Brodalumab was associated with rapid and significant improvements in signs and symptoms of moderate‐to‐severe plaque psoriasis, with a superior efficacy profile to what was observed with FAE in systemic‐naïve subjects over 24 weeks.

Brodalumab Versus Guselkumab in Patients with Moderate-to-Severe Psoriasis with an Inadequate Response to Ustekinumab: A Randomized, Multicenter, Double-Blind Phase 4 Trial (COBRA)

“…The rate of TEAEs observed for brodalumab in this trial was in line with that previously observed [ 21 , 22 ], and as also observed by Reich et al. [ 21 ], the greatest increase in reporting of TEAEs occurred during the initial weeks of treatment.…”

Efficacy and Safety of Dimethyl Fumarate in Patients with Moderate-to-Severe Plaque Psoriasis: Results from a 52-Week Open-Label Phase IV Clinical Trial (DIMESKIN 1)

“…This analysis through 52 weeks also suggests that DMF is effective for systemic-naïve patients in clinical practice and improves their quality of life. Mean absolute PASI scores described here at week 24 are in line with those previously published for FAEs [4.1 for DMF versus 4.6/5.1 (OC/mixed model repeated measures) for FAEs] [ 29 ]. Of note, a higher proportion of systemic-naïve patients achieved DLQI ≤ 1 (46.0%) at week 24 compared with previous published data for FAEs (14.8%) [ 30 ].…”

Brodalumab-Induced Eczematous Reactions in Psoriasis Patients: Management With Switching to Risankizumab

“…11 In a phase 4 trial (CHANGE) comparing the efficacy of brodalumab to oral fumaric acid esters in adults with psoriasis, one patient receiving brodalumab developed a serious adverse event and was hospitalized with “post trauma stasis dermatitis”. 12 However, It was not known whether it was associated with brodalumab. One other study reported a patient with brodalumab-associated generalized eczematous eruption who was eventually managed by topical steroids and 1 week delay of brodalumab without withdrawal.…”