Comorbid obesity is common and relevant to treatment

With the increase in treatment options, analyses of efficacy and adherence in relation to specific subpopulations of psoriasis patients are becoming increasingly important. According to a recent study, the treatment discontinuation rate is higher than average among overweight people. The pathophysiological relationships between psoriasis and obesity are complex and multifaceted.

The comorbidity rate is high in psoriasis patients, with approximately 70% of affected adults having at least one concomitant disease [1]. The prevalence of cardiovascular risk factors such as obesity, hypertension, diabetes, dyslipidemia, metabolic syndrome, and smoking is increased in psoriatic patients [2]. Consideration of metabolic disease in the choice of systemic treatment is an important factor, and it is now known that treatment outcome can be affected [3]. “In today’s era, with a multitude of approved, highly specific therapy options, predictive factors are playing an increasingly important role in personalized medicine,” said Julia-Tatjana Maul, MD, senior physician and head of the psoriasis consultation and clinical trials at University Hospital Zurich [4,5]. An interesting review has appeared in the British Journal of Dermatology on the question of whether there are predictive factors for the success of biologics therapy [6]. In this secondary analysis, referring to 16 cohort studies, it was shown that the treatment discontinuation rate was higher in women and in overweight patients. As a stratified analysis showed, treatment discontinuations were associated with adverse events in women and reduced efficacy in obesity.

IL23/Th17 axis in the joint pathogenesis of psoriasis and cardiometabolism.
A 2020 review supports the suggestion that upregulation of the IL23/Th17 pathway, in addition to lifestyle factors, leads to an increase in cardiometabolic psoriasis comorbidities [4,5]. In this context, there are new promising data on IL23p19 inhibition over a 52 week period [12]. It was shown that efficacy and safety of tildrakizumab are independent of metabolic comorbidities of psoriasis patients. This was the result of a post-hoc analysis of the two randomized-controlled phase III trials reSURFACE 1 and reSURFACE 2 [12,13]. Whether comorbidities are reduced by therapy is the subject of future long-term studies. Tildrakizumab, like guselkumab and risankizumab, is one of the selective interleukin23 (IL23) antagonists that can be used to treat patients with plaque psoriasis who cannot be adequately treated with other therapies.

Interaction structure of psoriasis and obesity: inflammatory mediators and other factors

Empirical data suggest that obesity is a predisposing factor for psoriasis through pro-inflammatory signaling pathways and promotes aggravation [7]. Studies have shown that psoriasis is mainly associated with central obesity, reflected by an increased waist-to-hip ratio [8,9]. In addition to mechanical protection and insulation, adipose tissue is an effective lipid storage organ in the body. Adipose tissue is classified as an endocrine organ that plays a central role in regulating metabolic homeostasis [10,11]. Obesity-induced dysregulation is thought to be an important component of psoriasis as well as other obesity-associated diseases. In morbid obesity, there is expansion of white adipose tissue and increased release of free fatty acids from white adipocytes, which in turn leads to increased serum fatty acid levels. Adipocytes and other cells in adipose tissue secrete various mediators involved in the regulation of organ function, metabolism, immunity, and inflammation. Mediators secreted by adipose tissue, adipokines, have pro-inflammatory properties and contribute to vulnerability to inflammation in obese individuals, which plays an important role in (cardio)metabolic comorbidities [10].

Also discussed is the question of a common genetic predisposition for the development of psoriasis and obesity. It is known that HLA-Cw6, a major psoriasis vulnerability gene, is also associated with obesity. Obese patients with this gene variant have a 35-fold higher incidence of psoriasis than other overweight individuals [5,8]. In normal-weight individuals with HLA-Cw6 positivity, the risk of psoriasis was 8.33 times higher than in the comparison group [9]. In addition to genetic dysregulation, lifestyle factors also play an important role. It is scientifically proven that psoriasis patients are at increased risk for unfavorable dietary habits, and obese psoriatic patients tend to engage in insufficient daily exercise [7].

Source: ZDFT 2020

Literature:

Augustin M, et al: Use of system therapeutics and biologics in guideline-based therapy of moderate to severe psoriasis vulgaris. PsoNet Magazine 2017/1.
Puig L, Kirby B, Mallbris L, Strohal R: Psoriasis beyond the skin: A review of the literature on cardiometabolic and psychological co-morbidities of psoriasis. Eur J Dermatol 2014; 24: 305-311
Torres T: Treating psoriasis in patients with metabolic comorbidities. Psoriasis treatment, slide presentation, Tiago Torres, MD, PhD, EADV Congress, Madrid, Oct. 12, 2019.
Maul JT: What’s new 2019/2020: inflammatory dermatoses. Julia-Tatjana Maul, MD, Zurich Dermatology Training Days (ZDFT), May 14-15, 2020.
Egeberg A, et al: The role oft he interleukin-23/Th17 pathway in cardiometabolic comorbidity associated with psoriasis. JEADV 2020, DOI: 10.1111/jdv.16273
Mourad A, et al. : Factors predicting persistence of biologic drugs in psoriasis: a systematic review and meta-analysis. Br J Dermatol 2019; 181(3): 450-458.
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Jin Y, et al: Combined effects of HLA-Cw6, body mass index and waist-hip ratio on psoriasis vulgaris in Chinese Han population. J Dermatol Sci 2008; 52: 123-129.
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Brembilla NC, Boehncke W-H: Dermal adipocytes’ claim for fame in psoriasis. Exp Dermatol 2016, Epub ahead of print.
Lebwohl MG, et al. Tildrakizumab efficacy and safety are not altered by metabolic syndrome status in patients with psoriasis: post-hoc analyses of phase 2 phase 3 randomized controlled studies (reSURFACE 1 and reSURFACE 2). J Am Acad Dermatol 2020; 82(2): 519-522.
Reich K, et al: Long-term efficacy and safety of tildrakizumab for moderate-to-severe psoriasis: pooled analyses of two randomized phase III clinical trials (reSURFACE1 and reSURFACE2) through 148 weeks. Br J Dermatol 2020; 182(3): 605-617.