Impact of Functional Polymorphisms on Drug Survival of Biological Therapies in Patients with Moderate-to-Severe Psoriasis.

Abstract

Biological therapies (BTs) indicated for psoriasis are highly effective; however, not all patients obtain good results, and loss of effectiveness is the main reason for switching. Genetic factors may be involved. The objective of this study was to evaluate the influence of single-nucleotide polymorphisms (SNPs) on the drug survival of tumor necrosis factor inhibitors (anti-TNF) medications and ustekinumab (UTK) in patients diagnosed with moderate-to-severe psoriasis. We conducted an ambispective observational cohort study that included 379 lines of treatment with anti-TNF (n = 247) and UTK (132) in 206 white patients from southern Spain and Italy. The genotyping of the 29 functional SNPs was carried out using real-time polymerase chain reaction (PCR) with TaqMan probes. Drug survival was evaluated with Cox regression and Kaplan-Meier curves. The multivariate analysis showed that the HLA-C rs12191877-T (hazard ratio [HR] = 0.560; 95% CI = 0.40-0.78; p = 0.0006) and TNF-1031 (rs1799964-C) (HR = 0.707; 95% CI = 0.50-0.99; p = 0.048) polymorphisms are associated with anti-TNF drug survival, while TLR5 rs5744174-G (HR = 0.589; 95% CI = 0.37-0.92; p = 0.02), CD84 rs6427528-GG (HR = 0.557; 95% CI = 0.35-0.88; p = 0.013) and PDE3A rs11045392-T together with SLCO1C1 rs3794271-T (HR = 0.508; 95% CI = 0.32-0.79; p = 0.002) are related to UTK survival. The limitations are the sample size and the clustering of anti-TNF drugs; we used a homogeneous cohort of patients from 2 hospitals only. In conclusion, SNPs in the HLA-C, TNF, TLR5, CD84, PDE3A, and SLCO1C1 genes may be useful as biomarkers of drug survival of BTs indicated for psoriasis, making it possible to implement personalized medicine that will reduce financial healthcare costs, facilitate medical decision-making and improve patient quality of life. However, further pharmacogenetic studies need to be conducted to confirm these associations.

• Authors: Cristina Membrive-Jiménez, Cristina Pérez-Ramírez, Salvador Arias-Santiago, Antonio Giovanni Richetta, Laura Ottini, Laura Elena Pineda-Lancheros, Maria Del Carmen Ramírez-Tortosa, Alberto Jiménez-Morales
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 24 Issue 10 (May 12 2023) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 37240048 (Publication Type: Observational Study, Journal Article)

Chemical References

• Tumor Necrosis Factor Inhibitors
• HLA-C Antigens
• Toll-Like Receptor 5
• Ustekinumab
• Adalimumab
• Tumor Necrosis Factor-alpha
• Infliximab
• CD84 protein, human
• Signaling Lymphocytic Activation Molecule Family
• SLCO1C1 protein, human
• Organic Anion Transporters

Topics

• Humans
• Tumor Necrosis Factor Inhibitors (therapeutic use)
• HLA-C Antigens
• Quality of Life
• Toll-Like Receptor 5
• Psoriasis (drug therapy, genetics, diagnosis)
• Ustekinumab (therapeutic use)
• Biological Therapy (methods)
• Adalimumab (therapeutic use)
• Tumor Necrosis Factor-alpha (therapeutic use)
• Infliximab (therapeutic use)
• Signaling Lymphocytic Activation Molecule Family
• Organic Anion Transporters