Can We Tell Patients That IL-23 and TNF-α Inhibition Are “Natural” Ways to Treat Psoriasis?

A major hurdle to the management of psoriasis is poor adherence to treatment. Patients may fear medications, even those that are highly safe and effective. Patients may prefer “natural” options, even though the term natural is not well defined. While patients’ preference for “natural” treatments may be a challenge to address, it may also be an opportunity.

Psoriasis exhibits a strong genetic component. Genetic association studies have identified single-nucleotide polymorphisms (SNPs) associated with psoriasis risk.^{1 -5} While normally we think of these alleles at these loci as causing psoriasis, we can also consider the SNPs associated with a lower risk of psoriasis as one of “nature’s ways” of protecting against the disease. Specifically, SNPs within the genes encoding p19, its receptor interleukin (IL)–23R, and tumor necrosis factor (TNF)–related genes have been associated with increased psoriasis risk, and therefore, other alleles at these loci can be thought of being associated with lower risk (Table 1).^1-5

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Table 1.

Summary of Single-Nucleotide Polymorphisms Associated With Psoriasis Risk.

Gene	Polymorphism	Odds Ratio a	Corresponding Medication(s)
IL12B	rs3212227	0.68	Ustekinumab
	rs6887695	0.70
IL23R	rs7530511	0.78	None
	rs11209026	0.63
IL23A	rs2066808	1.34 b	Guselkumab, tildrakizumab, risankizumab, mirikizumab
TNF-α	rs1800629	0.71	Adalimumab, infliximab etanercept
	rs361525	2.46 b

a

Reports odds ratio for non-risk-conferring allele unless otherwise noted.

b

Reports odds ratio for risk conferring allele.

By reducing key components of psoriasis pathogenesis, such as p19 and TNF-α, these SNPs can be thought of as one of “nature’s ways” of preventing psoriasis. Our treatment options that target these same pathways can be considered a “natural” approach to managing psoriasis, perhaps even targeting what may be the root cause of the problem in the pathogenesis of the disease. Presenting these treatments to patients in this context may help to alleviate concerns about using these pharmacologic interventions to treat their psoriasis.