The effect of weight on the efficacy of biologic therapy in patients with psoriasis

doi:10.1016/j.jaad.2007.11.011

Journal of the American Academy of Dermatology

Volume 58, Issue 3, March 2008, Pages 443-446

https://doi.org/10.1016/j.jaad.2007.11.011 Get rights and content

Background

The prevalence of obesity is rapidly increasing in the United States. Patients with psoriasis, in particular, tend to be above normal weight. Three of the 5 biologics used to treat psoriasis are fixed-dosed treatments: alefacept, etanercept, and adalimumab. Dosing regimens do not account for weight.

Objective

We attempted to determine whether the efficacy of the biologics is affected by weight.

Methods

We review the existing body of literature, including subgroup analyses, relating to efficacy and weight for infliximab, efalizumab, alefacept, and etanercept. No relevant literature was found for adalimumab.

Results

Weight-based dosed medications do not seem to lose efficacy with increasing weight. Both etanercept and alefacept may have compromised efficacy in heavier individuals.

Limitations

The data are limited to subgroup analyses and smaller studies, often with no statistical significance reported.

Conclusions

Additional studies are warranted, specifically designed to address the issue of obesity and response to therapy of the biologics. Alternative dosing for etanercept and alefacept should be further evaluated in patients above normal weight

Section snippets

Review of biologics and weight

Infliximab, a monoclonal antibody to TNF-α, is approved for psoriatic arthritis and is weight-dosed. The current recommended dose is 5-mg/kg infusion at weeks 0, 2, and 6, followed by infusions every 8 weeks. In a subgroup analysis of 3 randomized placebo-controlled trials for infliximab in 1462 patients with moderate to severe psoriasis, Reich et al⁷ found that patients who were overweight and obese achieved similar Psoriasis Area and Severity Index (PASI) 75 scores after 10 weeks of treatment

Conclusion

The link between obesity and psoriasis is complex and not fully understood. Obesity not only has effects on the body's cardiovascular, pulmonary, and endocrine system, but also on the immune system, which is implicated in the pathogenesis of psoriasis. Obese individuals have diminished T-cell populations and increased TNF-α concentrations,17, 18, 19, 20 both of which correct with significant weight loss.17, 18 Although immunologic parameters were not recorded, two case reports from the surgical

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Comorbid obesity and history of diabetes are independently associated with poorer treatment response to biologics at 6 months: A prospective analysis in Corrona Psoriasis Registry
2022, Journal of the American Academy of Dermatology
Psoriasis is associated with comorbid systemic metabolic disease.
To assess possible associations of comorbid obesity, history of diabetes, hypertension, and hyperlipidemia with response to biologic treatment at 6 months among patients in CorEvitas' Psoriasis Registry.
Participants included 2924 patients initiating biologic therapy (tumour necrosis factor inhibitors [TNFi], interleukin [IL]-17i, IL-12/23i, or IL-23i) with baseline and 6-month follow-up visits available. Logistic regressions resulted in adjusted odd ratios (OR) and 95% confidence intervals (CI) for achievement of response in select outcomes for those with obesity and history of diabetes, hypertension, and hyperlipidemia relative to those without each.
Overall, obesity reduced by 25% to 30% odds of achieving PASI75 (OR, 0.75; 95% CI, 0.64-0.88) and PASI90 (OR, 0.70; 95% CI, 0.59-0.81). History of diabetes reduced odds of achieving PASI75 by 31% (OR, 0.69; 95% CI, 0.56-0.85) and PASI90 by 21% (OR, 0.79; 95% CI, 0.63-0.98). Obesity was associated with lower response to TNFi and IL-17i classes. Independent of obesity, diabetes was associated with poorer outcomes when on IL-17i therapy and hypertension, to a lesser extent, when on the TNFi class. No significant associations were found in the hyperlipidemia group.
The study assessed only short-term effectiveness and small sample sizes limited the power to detect differences.
Assessment of comorbid disease burden is important for improved likelihoods of achieving treatment response with biologics.
IL-17A contributes to propagation of inflammation but does not impair adipogenesis and/or insulin response, in adipose tissue of obese individuals
2020, Cytokine
Adipose tissue is infiltrated with various immune cells, including Th17 lymphocytes and monocytes/macrophages, in obese individuals. We have previously demonstrated the role of obese adipose-derived stem cells (ob-ASC) and adipocytes (AD) in the mediation of inflammation through promotion of Th17 cells and activation of monocytes. Such an inflammation resulted in impaired ob-ASC adipogenesis and AD insulin response. In the present study, we investigated the role of IL-17A in the impairment of these functions.
With this aim, we used Secukinumab, a potent human anti-IL17A monoclonal antibody which has been approved for the treatment of some IL-17A related inflammatory diseases, notably Psoriasis. This antibody was added or not to phytohemagglutinin A-activated co-cultures of ob-ASC and mononuclear cells. The conditioning media of those co-cultures were harvested and added to AD ongoing differentiation from ob-ASC. Adipogenesis, insulin sensitivity and secretion of inflammatory cytokines were then measured using qRT-PCR, Western blots and ELISAs, respectively.
Surprisingly, we did not observe any direct effect of IL-17A on ob-ASC adipogenesis, despite sensitivity of ob-ASC to IL-17A. Moreover, IL-17A blockade, with the help of Secukinumab, did not lead to the recovery of adipogenesis and insulin response, when these functions were impaired by the presence of an inflammatory conditioning medium. However, the up-regulation of IL6 and IL1B mRNA expression by AD submitted to inflammatory conditioning medium was inhibited in the presence of Secukinumab, which indicates that IL-17A may play a role in the propagation of inflammation towards AD.
we show herein that IL-17A does not play a major role in the impairment of adipogenesis and/or insulin resistance mediated by an inflammatory environment, but contributes to the propagation of inflammation in human obese adipose tissues. This suggests a beneficial effect of anti-IL17A mAb in inflammatory pathologies, where obesity contributes to poorer response to biologic treatments.
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Citation Excerpt :
Psoriasis severity has been linked to obesity.130,131 The clinical response to biologics and systemic therapy used for the treatment of moderate-to-severe psoriasis appears to be less effective in patients with higher BMI (Tables IV and V).132-157 This observation might be associated with the higher treatment doses required to treat these patients.
Obesity is a worldwide major public health problem with an alarmingly increasing prevalence over the past 2 decades. The consequences of obesity in the skin are underestimated. In this paper, we review the effect of obesity on the skin, including how increased body mass index affects skin physiology, skin barrier, collagen structure, and wound healing. Obesity also affects sebaceous and sweat glands and causes circulatory and lymphatic changes. Common skin manifestations related to obesity include acanthosis nigricans, acrochordons, keratosis pilaris, striae distensae, cellulite, and plantar hyperkeratosis. Obesity has metabolic effects, such as causing hyperandrogenism and gout, which in turn are associated with cutaneous manifestations. Furthermore, obesity is associated with an increased incidence of bacterial and Candida skin infections, as well as onychomycosis, inflammatory skin diseases, and chronic dermatoses like hidradenitis suppurativa, psoriasis, and rosacea. The association between atopic dermatitis and obesity and the increased risk of skin cancer among obese patients is debatable. Obesity is also related to rare skin conditions and to premature hair graying. As physicians, understanding these clinical signs and the underlying systemic disorders will facilitate earlier diagnoses for better treatment and avoidance of sequelae.
Obesity in Autoimmune Diseases: Not a Passive Bystander
2019, Mosaic of Autoimmunity: The Novel Factors of Autoimmune Diseases
In the last decades, autoimmune diseases have experienced a dramatic increase in Western countries. The involvement of environmental factors is strongly suspected to explain this rise. Particularly, over the same period, obesity has followed the same outbreak. Since the exciting discovery of the secretory properties of adipose tissue, the relationship between obesity and autoimmunity and the understanding of the underlying mechanisms have become of major interest. Indeed, the fat tissue has been found to produce a wide variety of “adipokines,” involved in the regulation of numerous physiological functions, including the immune response. By conducting a systematic literature review, we extracted 329 articles regarding clinical, experimental, and pathophysiological data on the relationship between obesity, adipokines—namely leptin, adiponectin, resistin, visfatin—and various immune-mediated conditions, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes (T1D), psoriasis and psoriatic arthritis (PsA), and thyroid autoimmunity (TAI), especially Hashimoto thyroiditis. The strongest levels of evidence support an increased risk of RA (OR = 1.2–3.4), MS (OR = 2), psoriasis, and PsA (OR = 1.48–6.46) in obese subjects. A higher risk of IBD, T1D, and TAI is also suggested. Moreover, obesity worsens the course of RA, SLE, IBD, psoriasis, and PsA and impairs the treatment response of RA, IBD, psoriasis, and PsA. Extensive clinical data and experimental models demonstrate the involvement of adipokines in the pathogenesis of these autoimmune diseases. Obesity appears to be a major environmental factor contributing to the onset and progression of autoimmune diseases.
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View all citing articles on Scopus

: Funding sources: None.

: Disclosure: In the last 12 months, members of Dr Lebwohl's department have served at the drug companies listed below. Dr Lebwohl is also a consultant (or has pending agreements) for Abbott, Amgen, Astellas, Biogen Idec, Centocor, Connetics, Genentech, Novartis, Pfizer, Warner Chilcott, and 3M. In addition, members of Mount Sinai's Department of Dermatology hold patents for short-contact tazarotene therapy, excimer laser treatment vitiligo, and topical genistein. Finally, in the last 12 months, Dr Lebwohl has served as speaker for Abbott, Allergan, Amgen, Astellas, Biogen Idec, Centocor, Connetics, Novartis, Warner Chilcott, and 3M. Dr Clark has no conflicts of interest to declare.

View full text

ReviewThe effect of weight on the efficacy of biologic therapy in patients with psoriasis

Background

Objective

Methods

Results

Limitations

Conclusions

Section snippets

Review of biologics and weight

Conclusion

J Invest Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

Treatment of psoriasis

N Engl J Med

The skinny on psoriasis and obesity

Arch Dermatol

Impact of obesity and smoking on psoriasis presentation and management

Arch Dermatol

Consistency of infliximab response across subgroups of patients with psoriasis: integrated results from randomized controlled clinical trials

J Am Acad Dermatol

Population pharmacokinetics of efalizumab (humanized monoclonal anti-CD11a antibody) following long-term subcutaneous weekly dosing in psoriasis subjects

J Clin Pharmacol

Review
The effect of weight on the efficacy of biologic therapy in patients with psoriasis