Pharmacogenetics and Pharmacogenomics in Moderate-to-Severe Psoriasis

Abstract

Pharmacogenetics is the study of variations in DNA sequence related to drug response. Moreover, the evolution of biotechnology and the sequencing of human DNA have allowed the creation of pharmacogenomics, a branch of genetics that analyzes human genes, the RNAs and proteins encoded by them, and the inter-and intra-individual variations in expression and function in relation to drug response. Pharmacogenetics and pharmacogenomics are being used to search for biomarkers that can predict response to systemic treatments, including those for moderate-to-severe psoriasis. Psoriasis is a chronic inflammatory disease with an autoimmune contribution. Although its etiology remains unknown, genetic, epigenetic, and environmental factors play a role in its development. Diverse systemic and biologic therapies are used to treat moderate-to-severe psoriasis. However, these treatments are not curative, and patients exhibit a wide range of responses to them. Moderate-to-severe psoriasis is usually treated with systemic immunomodulators such as acitretin, ciclosporin, and methotrexate. Anti-tumor necrosis factor (TNF) drugs (adalimumab, etanercept, or infliximab) are the first-line treatment for patients resistant to conventional systemic therapies. Although these therapies are very efficient, around 30-50% of patients have inadequate response. Ustekinumab is a monoclonal antibody that targets interleukin (IL)-12 and IL-23 and is used for moderate-to-severe psoriasis. New drugs (apremilast, brodalumab, guselkumab, ixekizumab, and secukinumab) have recently been approved for psoriasis. However, response rates to systemic treatments for moderate-to-severe psoriasis range from 35 to 80%, so it is necessary to identify non-invasive biomarkers that could help predict treatment outcomes of these therapies and individualize care for patients with psoriasis. These biomarkers could improve patient quality of life and reduce health costs and potential side effects. Pharmacogenetic studies have identified potential biomarkers for response to biologic treatments for moderate-to-severe psoriasis. These biomarkers need to be validated in clinical trials involving large cohorts of patients before they can be translated to the clinic. We review pharmacogenetics and pharmacogenomics studies for the treatment of moderate-to-severe plaque psoriasis.

Circular RNA Expression Profile and Analysis of Their Potential Function in Psoriasis

“…T cell-and immune active molecules-mediated inflammatory reactions play an important role. To date, different systematic drugs and biologic therapies have been used to treat moderate to severe psoriasis [28]. However, these treatments are not curative, and the study of the pathogenesis of psoriasis is ongoing.…”

The role of the interleukin‐23/Th17 pathway in cardiometabolic comorbidity associated with psoriasis

“…19 Despite the primary cause of psoriasis being unknown, some genetic factors are acknowledged risk factors for its development. 20,21 Further, a dysregulated immune response involving keratinocytes, vascular endothelial cells, Th17, Th1, Treg, cd-T cells, DCs, macrophages, neutrophils, mast cells and NK cells underlies the pathogenesis of psoriasis. 19,22,23 The primary consideration of psoriasis as a Th1/Tc1-mediated disease 19,24 was supported by efficacy of monoclonal antibodies targeting p40 subunit of IL-12, the cytokine considered crucial in the Th1 differentiation.…”

Precision therapy for psoriasis patients

“…Эффективность лечения ингибиторами TNF-α возрастает при выявлении полиморфных вариантов генов, кодирующих мембранный белок семейства рецепторов фактора некроза опухоли альфа (TNFRSF1B), белок, вовлеченный в убиквитин-связанный воспалительный каскад (TNFAIP3), провоспалительные цитокины (IL-23R, IL-17F), белки рецепторов иммуноглобулинов (FCGR2A, FCGR3A) [30].…”