Pharmacogenetics of etanercept: role of TNF-α gene polymorphisms in improving its efficacy.
Expert Opin Drug Metab Toxicol
; 10(12): 1703-10, 2014 Dec.
Article
en En
| MEDLINE
| ID: mdl-25300969
ABSTRACT
INTRODUCTION:
During the last decade, many new biological immune modulators have entered the market as new therapeutic principles. Biologics, including TNF-α inhibitors, are the new frontier in the treatment of immune-mediated or inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, ankylosing spondylitis, systemic sclerosis, disseminated granuloma annulare, psoriasis and/or psoriatic arthritis. TNF-α inhibitors have demonstrated efficacy and are well tolerated in large, randomized, controlled clinical trials. However, a substantial proportion of patients do not respond to these agents and potential adverse drug reactions may be associated with its use. AREAS COVERED Pharmacogenetics has the potential of increasing drug efficiency by identifying genetic factors responsible for lack of response or toxicities to TNF-α inhibitors. In this review, we analyze the influence of several polymorphisms upon the efficacy and safety of TNF-α inhibitors. EXPERT OPINION Several polymorphisms have been proven to influence the response to etanercept. Among them, single nucleotide polymorphisms (SNPs) -308 G/G, -857 C/T, +489 GG and GA, HLA-DRB1-encoding SE (allele *0404 and allele *0101) favor the response to etanercept, whereas SNP -308 A/A and TNFR1A AA decrease the response. Large clinical studies are needed to confirm the relevance of these associations in order to tailor treatment and to decrease unnecessary toxicity.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Farmacogenética
/
Inmunoglobulina G
/
Factor de Necrosis Tumoral alfa
/
Receptores del Factor de Necrosis Tumoral
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Polimorfismo de Nucleótido Simple
/
Antiinflamatorios
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
/
Systematic_reviews
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Expert Opin Drug Metab Toxicol
Asunto de la revista:
METABOLISMO
/
TOXICOLOGIA
Año:
2014
Tipo del documento:
Article