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).

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.

Increased number and frequency of group 3 innate lymphoid cells in nonlesional psoriatic skin.

BACKGROUND: Psoriasis is a common immune-mediated inflammatory disease that affects the skin and joints. The interleukin (IL)-23/IL-17A axis and IL-22 play key roles in the pathogenesis of psoriasis. IL-23-responsive innate lymphoid cells (ILCs) with a high capacity to produce IL-17 and/or IL-22 have recently been identified and associated with inflammatory bowel diseases. The occurrence and role of ILCs in human skin are poorly understood. OBJECTIVES: To describe the prevalence of the different ILC subpopulations in skin from healthy controls and patients with psoriasis or allergy to nickel. METHODS: Skin biopsies were taken from healthy skin, nonlesional and lesional psoriatic skin, and nickel- and petrolatum-exposed skin from patients with contact allergy to nickel, and lymphocytes were isolated. The cells were stained and characterized by flow cytometry. Cytokine and ligand mRNA expression were measured by quantitative polymerase chain reaction. RESULTS: We found that members of the three groups of ILCs were present in human skin. Remarkably, the number and frequency of RORγt(+) CD56(+) ILC3s, which are known to produce IL-22, were elevated in both nonlesional and lesional skin from patients with psoriasis compared with healthy skin and skin from patients with contact allergy to nickel. Furthermore, skin ILCs expressed high levels of the natural killer receptor NKG2D. NKG2D binds to stress-induced ligands, including major histocompatibility complex class I-related chain A, which we found to be strongly upregulated in lesional skin from patients with psoriasis. CONCLUSION: These results show that ILCs are present in human skin and indicate that RORγt(+) CD56(+) ILC3 may be involved in the pathogenesis of psoriasis.