INDIVIDUAL ARTICLE: Psoriasis and Obesity: Optimizing Pharmacologic Treatment and Lifestyle Interventions

January 2025 | Volume 24 | Issue 1 | 491722s4 | Copyright © January 2025


Published online December 31, 2024

Lily Guo BSa, Leon Kircik MDb-f, April W. Armstrong MD MPHg

aDuke University School of Medicine, Durham, NC
bDepartment of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY
cDepartment of Dermatology, Indiana University School of Medicine, Indianapolis, IN
dPhysicians Skin Care, PLLC, Louisville, KY
eDermResearch, PLLC, Louisville, KY
fSkin Sciences, PLLC, Louisville, KY
gDivision of Dermatology, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA

Abstract
Obesity is a metabolic disease that is marked by excessive fat accumulation and is objectively defined as a body mass index (BMI) ≥30 kg/m2. Obesity is associated with several other comorbidities, including psoriasis, which is a chronic autoimmune skin disease. Adipocytes produce pro-inflammatory signaling molecules, namely adipokines and classic cytokines, that drive increased inflammation axnd may contribute to the pro-inflammatory pathways driving psoriasis disease pathogenesis. Optimizing dermatologic management of obese patients with psoriasis may be challenging due to the effect of comorbid obesity on the pharmacokinetics of systemic therapies. Biologic therapy is a mainstay of psoriasis treatment in these patients. The IL-17 and IL-23 inhibitor classes, including those targeting the IL-17 receptor (brodalumab), IL-17 cytokine antagonists (secukinumab, ixekizumab, bimekizumab), and IL-23 cytokine antagonists (guselkumab, risankizumab, tildrakizumab). In general, the most efficacious biologics that work well for generalized plaque psoriasis also tend to work well for most obese psoriasis patients. For example, brodalumab, an IL-17 receptor inhibitor, demonstrated comparable efficacy across BMI categories in both clinical trial and real-world practice data. In addition to psoriasis-specific therapy, interventions targeted at weight loss may help treat obesity and decrease psoriasis disease severity. These interventions include glucagon-like peptide-1 receptor agonist therapy, caloric restriction, and different forms of bariatric surgery. Clinical trials and real-world data evaluating the efficacy of different biologic treatments and weight-loss interventions in the treatment of obese psoriasis patients should be used to support clinical decision-making for treatment options.

J Drugs Dermatol. 2025;24:1(Suppl 1):s4-14.

INTRODUCTION

Defining Obesity

Obesity is a multifactorial disease with a rapidly increasing global prevalence.1 Its etiology is driven by a chronic imbalance between energy intake and energy expenditure.1 Excess energy is stored in adipocytes, which undergo hyperplasia and hypertrophy over time. The resulting excess fat stores contribute to a myriad of pathologies in different organ systems.

Obesity is defined by the World Health Organization (WHO) as "abnormal or excessive fat accumulation [that] presents a health risk" and measured by body mass index (BMI).2 BMI is calculated by dividing a person's weight in kilograms by their height in square meters. Increased BMI can indicate an increased degree of body fatness.3 For adults, the WHO defines normal weight as a BMI of 18.5 to 24.9 kg/m2, overweight as BMI greater than or equal to 25 kg/m2, and obese as BMI greater than or equal to 30 kg/m2. Definitions of obesity can further be subdivided based on central vs peripheral distributions of adipose tissue. Obese individuals with abdominal circumferences greater than or equal to 40 inches (102 cm) in men and greater than or equal to 35 inches (88 cm) in women are classified as having central obesity.4 However, in the setting of healthcare and clinical trial research, BMI is the most commonly used metric to define obesity.5

Obesity Increases Risk of Comorbid Conditions

Obesity is a proinflammatory state that increases a patient’s risk for cardiovascular disease, diabetes mellitus, certain malignancies, musculoskeletal diseases, liver disease, and psychiatric comorbidities and decreases a patient's