Reviewing the Link Between Psoriasis and High Body Mass Index: Focus on IL-17–Mediated Pathology and Anti–IL-17 Therapy

Vollständiger Abstract

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Introduction Psoriasis and obesity frequently coexist and have a bidirectional relationship: high body mass index (BMI) seen in obesity is a risk factor for psoriasis, and patients with psoriasis are more likely to have obesity. Further, patients with psoriasis and high BMI often experience reduced efficacy with biologic therapies; as such, some biologics offer weight-based dosing. Brodalumab, the only interleukin-17 (IL-17) receptor A blocker approved for moderate-to-severe plaque psoriasis, blocks downstream signaling of multiple IL-17 isoforms (IL-17A, IL-17F, IL-17C, IL-17E, and IL-17 A/F) and is administered at the same dose regardless of body weight. Here we summarize the role of IL-17 in obesity and psoriasis and the clinical trial efficacy and safety of brodalumab in patients with obesity. Methods A qualitative literature review was conducted to identify overlapping IL-17–mediated mechanisms of disease between obesity and psoriasis. Post hoc analysis of efficacy and safety in brodalumab-treated participants with high BMI was summarized for the phase 3 AMAGINE trials (NCT01708603, NCT01708629). Outcomes included Psoriasis Area and Severity Index (PASI) scores and treatment-emergent adverse events (TEAEs) and were reported for participants who received continuous brodalumab 210 mg every 2 weeks throughout the studies (n=248). Results Both obesity and psoriasis pathogenesis involves upregulation of the IL-17–producing T cell pathway. In obesity, adipose tissue produces proinflammatory cytokines and other bioactive molecules, which promote activation of IL-17–secreting T cells, leading to the creation of a general proinflammatory environment. IL-17, together with other cytokines, leads to psoriatic disease manifestation by inducing downstream keratinocyte proliferation, increased angiogenic mediators, endothelial adhesion molecule expression, and infiltration of immune cells into lesional skin. Per a post hoc analysis of the AMAGINE-2 and -3 trials, efficacy did not markedly differ by BMI, with week 12 PASI 100 rates of 54% and 50% and week 52 rates of 73% and 65% in patients without obesity (BMI