Tumour necrosis factor (TNF)alpha-308 G/G promoter polymorphism and TNF alpha levels correlate with a better response to adalimumab in patients with rheumatoid arthritis

Cuchacovich M.; Soto L.; Edwardes, M; Gutiérrez M; Llanos, C.; Pacheco, D.; Sabugo, F; Alamo, M; Fuentealba, C; Villanueva, L; Gatica H.; Schiattino I.; Salazar, L; Catalan, D; Valenzuela O.

Abstract

Objective: To investigate the influence of -308 tumour necrosis factor-α (TNFα) promoter polymorphism and circulating TNFα levels in the clinical response to adalimumab treatment in patients with rheumatoid arthritis (RA). Methods: Eighty-one patients with active RA were genotyped for the -308 TNFα polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and subdivided into two groups for each polymorphism (G/A and G/G genotype). All received 40 mg of adalimumab subcutaneously every other week. We compared the groups' clinical responses to adalimumab at 8, 16, and 24 weeks using the Disease Activity Score in 28 joints (DAS28). Results: Both groups showed a significant improvement from baseline. A significant difference between groups was found at week 24. We found that 88.2% of G/G versus 68.4% of G/A for the -308 polymorphism were DAS28 responders (p = 0.05). The score improvement at week 24 was 2.5±1.3 in the G/G group and 1.8±1.3 in the G/A group for the -308 polymorphism (p = 0.04). The median of serum TNFα levels of the G/A group were lower than those of the G/G group, and statistically different at weeks 8 and 24 (p<0.039 and p<0.043). When comparing baseline levels to those achieved at 8, 16, and 24 weeks for the whole group, only responder patients showed a statistically significant overall increase in TNFα over time (p<0.000001). Conclusion: A relationship between DAS28 improvement, the -308 G/G polymorphism, and increased circulating TNFα levels was found in Chilean RA patients treated with adalimumab. © 2006 Taylor & Francis on license from Scandinavian Rheumatology Research Foundation.

Más información

Título según WOS: Tumour necrosis factor (TNF)alpha-308 G/G promoter polymorphism and TNF alpha levels correlate with a better response to adalimumab in patients with rheumatoid arthritis
Título según SCOPUS: Tumour necrosis factor (TNF)a -308 G/G promoter polymorphism and TNFa levels correlate with a better response to adalimumab in patients with rheumatoid arthritis
Título de la Revista: SCANDINAVIAN JOURNAL OF RHEUMATOLOGY
Volumen: 35
Número: 6
Editorial: TAYLOR & FRANCIS LTD
Fecha de publicación: 2006
Página de inicio: 435
Página final: 440
Idioma: English
URL: http://informahealthcare.com/doi/abs/10.1080/03009740600904284
DOI:

10.1080/03009740600904284

Notas: ISI, SCOPUS