Systemic drug therapy in the obese patient with psoriasis

Should a patient’s Body Mass Index (BMI) influence the choice of a systemic drug in the treatment of psoriasis and psoriatic arthritis?  A recent report suggests that the answer is ‘Yes’¹.

There is a strong and consistent association between obesity and psoriasis; obese patients are more likely to develop psoriasis and its severity increases with increasing body weight. Psoriatic arthritis is a common comorbidity of psoriasis.  Whilst the link between psoriasis and obesity is still not entirely clear, it appears to be related to shared pathophysiological pathways where local and systemic inflammation promote each other.  Psoriasis is an inflammatory autoimmune disease and adipose tissue is a reservoir of pro-inflammatory cytokines. 

Management of psoriasis in obese subjects is made more difficult, because many commonly used systemic drugs, such as cyclosporine and acitretin, are less effective and carry a greater risk of adverse events in obese subjects.   Moreover, several studies have demonstrated a better response to anti-tumour necrosis factor (TNF) drugs (e.g. adalimumab) in normal weight patients, compared with obese patients.  A key variable in this weight-associated variation in response to therapy, is the rate of drug clearance.  Individuals weighing more than 100kg clear the drug 55% faster and have 35% greater volume of distribution, both of which lead to lower drug concentrations².   Also relevant is the fact that anti-TNF agents – unlike IL-17 inhibitors – have been shown to cause weight gain, thus reducing efficacy even further. 

Secukinumab, on the other hand, is a monoclonal antibody that selectively binds to and neutralizes IL-17A.  It has been shown to be effective in the treatment of psoriasis, ankylosing spondylitis, and psoriatic arthritis.  Very importantly, its efficacy appears to be similar across all body weight groups.  

NB:  Methotrexate carries a higher risk of fatty liver and hepatic fibrosis in obese patients and should be avoided.

Key Points

• Obese subjects have a high prevalence of psoriasis and are less efficiently treated with systemic agents, due to both reduced efficacy and increased risk of adverse events.
• Anti-TNF agents (e.g. adalimumab) may lead to weight gain, further reducing the benefits of treatment
• Methotrexate should be avoided in obese patients with psoriasis and psoriatic arthritis
• Secukinumab is an IL-17a inhibitor, which does not lead to weight gain and whose beneficial effects are independent of body weight
• Secukinumab is effective in obese patients with psoriasis and psoriatic arthritis

References

1. Tiberio R, Graziola F, et al.  Secukinumab for Psoriasis in Obese Patients: Minireview and Clinical Experience.  Case Rep Dermatol 2019;11: 29–37
2. Thibodaux RJ, Triche MW, Espinoza LR. Ustekinumab for the treatment of psoriasis and psoriatic arthritis: a drug evaluation and literature review. Expert Opin Biol Ther. 2018; 18: 821–7.