Psoriasis is a chronic inflammatory skin pathology of autoimmune origin and unknown etiology. There are various therapies for treating it, including a wide range of biopharmaceuticals indicated in moderate-to-severe psoriasis. Depending on their therapeutic target, they are classified as tumor necrosis factor inhibitors (anti-TNF) or cytokine inhibitors (interleukin-12, 23, and 17 antagonists). Although they have proved effective and safe, in clinical practice, many patients show a short- and long-term suboptimal response and even varying degrees of toxicity. This variability in response may be influenced by genetic factors, such as polymorphisms in the genes involved in the pathological environment, metabolism or mechanism of action of the drug that could affect the effectiveness and toxicity of biological therapies. This review assesses pharmacogenetic studies of the impact of genetic factors on response to biopharmaceuticals and toxicity in patients diagnosed with moderate-to-severe psoriasis. The results suggest that polymorphisms detected in the HLA genes, in genes that encode cytokines (TNF, IL genes, TNFAIP3), transporters (PDE3A-SLCO1C1, SLC12A8), receptors (TNFRSF1B, CD84, FCGR2A and FCGR3A, IL17RA, IL23R, TLR genes, PGLYRP4) and associated proteins (TNFAIP3, LY96, TIRAP, FBXL19), as well as other genes implicated in the pathogenesis of psoriasis (CDKAL1, CARD14, PTTG1, MAP3K1, ZNF816A, GBP6, CTNNA2, HTR2A, CTLA4, TAP1) can be used in the future as predictive markers of treatment response and/or toxicity with biological therapies in patients diagnosed with moderate-to-severe psoriasis, tailoring treatment to the individual patient.

Dermatologic pathologies are the fourth most common cause of non-fatal disease worldwide; however, they produce a psychosocial, economic, and occupational impact equal to or greater than other chronic conditions. The most prevalent are actinic keratosis, followed by basal-cell carcinoma, in a lesser proportion acne vulgaris, psoriasis, and hidradenitis suppurativa, among others, and more rarely dermatitis herpetiformis. To treat actinic keratosis and basal-cell carcinoma, 5-fluorouracil (5-FU) 0.5% is administered topically with good results, although in certain patients it produces severe toxicity. On the other hand, dapsone is a drug commonly used in inflammatory skin conditions such as dermatitis herpetiformis; however, it occasionally causes hemolytic anemia. Additionally, biologic drugs indicated for the treatment of moderate-to-severe psoriasis and hidradenitis suppurativa have proved to be effective and safe; nevertheless, a small percentage of patients do not respond to treatment with biologics in the long term or they are ineffective. This interindividual variability in response may be due to alterations in genes that encode proteins involved in the pathologic environment of the disease or the mechanism of action of the medication. Pharmacogenetics studies the relationship between genetic variations and drug response, which is useful for the early identification of non-responsive patients and those with a higher risk of developing toxicity upon treatment. This review describes the pharmacogenetic recommendations with the strongest evidence at present for the treatments used in dermatology, highlighting those included in clinical practice guides. Currently, we could only find pharmacogenetic clinical guidelines for 5-FU. However, the summary of product characteristics for dapsone contains a pharmacogenetic recommendation from the United States Food and Drug Administration. Finally, there is an enormous amount of information from pharmacogenetic studies in patients with dermatologic pathologies (mainly psoriasis) treated with biologic therapies, but they need to be validated in order to be included in clinical practice guides.